Cancer Translational Medicine

: 2017  |  Volume : 3  |  Issue : 3  |  Page : 87--95

Stemness-related markers in cancer

Wenxiu Zhao1, Yvonne Li2, Xun Zhang1,  
1 Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
2 Department of Medical Oncology, Dana-Farber Institute and Harvard Medical School, Boston, MA, USA

Correspondence Address:
Dr. Xun Zhang
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, BUL457, Boston, MA 02114


Cancer stem cells (CSCs), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute toward a “stemness” phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers, and signaling pathways.

How to cite this article:
Zhao W, Li Y, Zhang X. Stemness-related markers in cancer.Cancer Transl Med 2017;3:87-95

How to cite this URL:
Zhao W, Li Y, Zhang X. Stemness-related markers in cancer. Cancer Transl Med [serial online] 2017 [cited 2020 Jul 14 ];3:87-95
Available from:

Full Text


Individual tumors consist of a mixed cell population that differs in function, morphology, and molecular signatures. These tumors reside in and interact with their microenvironment, which consists of a wide variety of cell types and cellular structures, such as immune cells, fibroblasts, blood vessels, and extracellular matrix. Tumor cells themselves can be of multiple clonal populations, each having accumulated unique molecular alterations over the course of tumor development and growth. In addition, tumor cells that are similar at genetic level may have distinct modes of epigenetic regulation, further increasing the functional heterogeneity.

It has been hypothesized that only a small subset of tumor cells are capable of initiating and sustaining tumor growth; they have been termed cancer stem cells (CSCs).[1] To date, CSCs have been isolated from many organs and confirmed to have stem cell-like abilities such as self-renewal, multilineage differentiation, and expression of stemness-related markers;[2],[3] some of these features are even confirmed by single-cell analysis.[4] These cells may also play a role in disease recurrence after treatment and remission. As such, targeting of CSCs is currently an active area of therapeutic development.

CSCs are classified by the expression of stemness-related markers, which have been identified in embryonic stem cells (ESCs) and adult stem cells, the two main types of human stem cells. Here, we summarize the current knowledge about molecular markers and pathways that are not only involved in normal stem-cell maintenance and self-renewal but also regulate the stemness of CSCs. Investigation of these features may help elucidate the mechanism of CSC-driven tumorigenesis and lead to novel approaches for CSC-targeted cancer therapies.

 Stemness-Related Transcriptional Factors in Cancers

Takahashi and Yamanaka [5] showed in 2006 that pluripotent stem cells could be obtained from mouse embryonic fibroblasts by combined expression of four transcriptional factors (TFs) – now named the Yamanaka factors (OCT4, c-Myc, SOX2, and KLF4). Induced pluripotent stem cells can now be derived from a wide range of somatic cells through the overexpression of a cocktail of TFs [6] or a combination of TF expression with chemical compounds.[7],[8] Moreover, somatic cells can now be directly reprogrammed into entirely different cell types [9] through the expression of lineage-specific sets of transcription factors. Yamanaka's seminal discovery has introduced the concept that the fate of adult somatic cells can be controlled through TF expression. From another perspective, expression of stem-cell-specific TFs can provide a signature for characterizing cell type as well as indicating their functional roles.

There are currently approximately 25 TFs that have been reported to be expressed in stem cells. Of them, OCT4, SOX2, KLF4, Nanog, and SALL4 comprise a core regulatory network for ESC maintenance and self-renewal. These TFs are highly expressed in ESCs; in contrast, they are mainly silenced in normal somatic cells, except in small groups of adult stem-cell populations. Increasing evidence has shown that embryonic-specific TFs are abnormally expressed in human tumor samples,[10],[11] suggesting the presence of CSCs. Retrospective studies on patient cohorts have also associated TF expression with survival outcomes in specific tumor types, suggesting that TF expression levels may also be useful for assessing patient prognosis.[12] Thus, detecting the expression level of these TFs, for example, by immunohistochemistry staining, can aid in tumor diagnosis, classification, and therapeutic strategies.

A summary of these CSC TFs is shown in [Table 1]. These TF markers are also classified by tissue type as shown in [Table 2]. A few examples are listed here.{Table 1}{Table 2}


OCT4 expression has been detected in human brain, lung, bladder, ovarian, prostate, renal, testicular tumors, and leukemia,[12] by both reverse transcription-polymerase chain reaction and immunohistochemistry. Furthermore, high expression of OCT4 has been associated with poor prognosis in bladder cancer,[13],[14] prostate cancer,[15] medulloblastoma,[16] and esophageal squamous cell carcinoma (ESCC).[17]


SOX2 has been found in brain, breast, lung, liver, prostate, and testicular tumors,[12],[18],[19] and its expression has been correlated with poor prognosis in stage I lung adenocarcinoma,[18] squamous cell carcinoma,[20],[21] gastric carcinoma,[22],[23],[24] small cell lung cancer,[25],[26],[27],[28] and ovarian carcinoma.[29],[30]


KLF4 has been found to be expressed in brain, breast, head and neck, oral, prostate, and testis tumors, as well as in leukemia and myeloma.[12] Expression of KLF4 can also be a prognostic predictor for colon cancer [31] and head-neck squamous cell carcinoma.[24],[32] In addition, nuclear localization of KLF4 has been associated with the aggressive phenotype of early stage of breast cancer,[33] as well as worse prognosis in nasopharyngeal [34] and oral cancers.[53]


Nanog has been shown to be expressed in brain, breast, prostate, colon, liver, and ovarian tumors.[40] High expression of Nanog promotes the epithelial-mesenchymal transition (EMT),[41] which is an important developmental process for cancer cells to obtain stem-cell characteristics. Nanog has also been associated with poor prognosis in breast,[42] colorectal,[43],[44] gastric,[45] lung,[46],[47] ovarian,[48] and liver cancers.[54]


SALL4 expression has been detected in breast, liver, colon, ovarian, and testis cancers and leukemia.[49],[55] The expression of SALL4 has been studied as a poor prognosis marker in hepatocellular carcinoma,[50],[51] gliomas,[52] and myelodysplastic syndromes.[35]


C-Myc is an important TF both in stem cells and cancers. As one of the most studied oncogenes, overexpression of C-Myc has been shown to cause tumorigenesis in mouse models. Up to 70% of human cancers exhibit c-Myc overexpression, including brain, breast, colon, head and neck, pancreas, prostate, renal, salivary gland, and testis tumors, as well as leukemia and lymphoma.[12],[36],[37] C-Myc expression has also been correlated with poor prognosis in hepatocellular carcinoma [38] and early carcinoma of uterine cervix.[39],[56]

 Stemness-Related Surface Markers in Cancers

Cell surface proteins provide a feasible way for isolating and studying different cell types by flow cytometry or magnetic sorting. In addition, they are amenable for specific targeting, which is useful for disease monitoring and therapeutic delivery. Similar to stemness-related transcription factors, many surface markers that are highly expressed in stem cells are also expressed in human cancers as TRA-1-60, SSEA-1, EpCAM, ALDH1A1, Lgr5, CD13, CD19, CD20, CD24, CD26, CD27, CD34, CD38, CD44, CD45, CD47, CD49f, CD66c, CD90, CD166, TNFRSF16, CD105, CD133, CD117/c-kit, CD138, CD151, and CD166. [Table 2] describes most of the stemness-related surface markers and the tumor types they have been found to be expressed in. Among them, CD44 and CD133 are the most widely used markers in CSC research and are also therapeutic targets in cancers.

CD44 is a transmembrane glycoprotein that plays different roles in cell division, migration, adhesion, and signaling.[57] It is normally expressed in both fetal and adult hematopoietic stem cells, and on binding to hyaluronic acid, its primary ligand, CD44 mediates cell-cell communication and signal transaction. CD44 is highly expressed in many types of cancers including bladder, breast, colon, gastric, glioma, head and neck, osteosarcoma, ovarian, pancreatic, and prostate cancers, as well as leukemia.[58],[59] CD44 is being studied as a therapeutic target in metastasizing tumors such as breast and colon cancer [60],[61] and also in leukemia.[62]

CD133 is another transmembrane glycoprotein and specifically localizes to cellular protrusions. CD133 is reported to be expressed in hematopoietic stem cells, endothelial progenitor cells, glioblastoma, and neuronal and glial stem cells,[63],[64] and it is also involved in cell growth and development.[65] Almost all tumor types can be detected with CD133 expression, and CD133+ tumor cells show stem-cell-specific characteristics such as self-renewal, differentiation, and tumor formation in NOD-SCID mouse model.[66] After injection into immune-compromised mice, CD133+ cells also show chemo- and radio-resistance.[66] Studies have been performed to use CD133 as a potential therapeutic target in colon cancer,[67] ovary cancers,[68] and metastatic melanoma.[69] CD133 has also been used as a target for drug delivery.[70]

There are a number of other CSC surface markers that appear to function in specific types of tumors. For examples, SSEA-1 has been shown to be expressed in human colonic adenocarcinoma and glioblastoma.[71],[72] Similarly, TRA-1-60 has been associated with prostate tumors.[73] Lgr5 has been shown to be expressed in head and neck, colon, and gastric tumors.[74],[75] CD90 has been detected in high-grade human glioma,[76],[77] as well as liver [78] and lung tumors;[79],[80] while CD117 has been used as a CSC marker in leukemia [81],[82] and gastrointestinal stromal tumor,[83] as well as oral squamous cell carcinomas [84],[85] and ovarian tumors.[86],[87] CD117 has been shown to be overexpressed in hepatocellular [88] and pancreatic carcinoma.[89] CD24 has been used in combination with CD44 in breast cancer cell lines to show that CD44+/CD24- cancer cells exhibit drug resistance and invasive properties.[90],[91],[92] Studies have also shown that CD24 can be used as an independent prognostic marker nonsmall cell lung cancer [93],[94] and ovarian cancer.[95]

 Other Important Stemness-Related Markers

There are a number of stemness-related markers that are neither TFs nor cell surface proteins, which include aldehyde dehydrogenase (ALDH), Bmi-1, Nestin, Musashi-1, TIM-3, and CXCR. The ubiquitous family of ALDH enzymes catalyzes the irreversible oxidation of cellular aldehydes in the cytoplasm. High activity of ALDH enzymes has been found in ESCs, adult hematopoietic and neural stem cells, as well as CSCs. ALDH activity in CSCs has been attributed to ALDH1A1 expression, which can regulate stem-cell self-protection, differentiation, and population expansion. ALDH has been reported to have prognostic significance in head and neck squamous cell [96] and ESCC.[97] It is also being pursued as a therapeutic target in ovarian [98],[99] and nonsmall cell lung cancers.[100]

BMI1 is a protein required for hematopoietic stem-cell self-renewal [101] and neural stem cells.[102] Drug-induced expression of BMI1 has been shown to enhance stem-cell populations in head and neck cancer models.[103] BMI1 has been reported as a marker for poor prognosis in oligodendroglial tumors [104] and breast cancer.[105],[106] Nestin and Musashi-1 have been detected in neural stem cells,[107] where they both play an important role in stem-cell self-renewal and maintenance. Nestin expression has been shown in transformed cells of various human malignancies, correlating with the clinical course of some diseases.[108] Furthermore, coexpression of Nestin with other stem-cell markers was described as a CSC phenotype.[109] Nestin was reported as a potential target for tumor angiogenesis.[110],[111] Musashi-1 signaling was also detected in hematopoietic stem cells, and it is being investigated as a potential therapeutic target and diagnostic marker for lung cancer.[112]

Chemokines are small peptide molecules secreted by cells that affect the movement of neighboring cells, thus mediating cellular homing and migration. They are crucial for normal physiological functions and are found to be dysregulated in cancers. The chemokine CXCL12 (SDF-1) and its receptor CXCR4 regulate cellular chemotaxis, cell adhesion, survival, proliferation, and gene transcription through multiple divergent pathways. CXCL12/CXCR4 interactions were shown to play an important role in the migration of hematopoietic stem cells.[113] CXCR4 is overexpressed in more than twenty cancer types, with discovered roles in tumor growth, invasion, angiogenesis, metastasis, relapse, and therapeutic resistance.[114] CXCR4 antagonists have been shown to disrupt tumor-stromal cell interactions, sensitize cancer cells to cytotoxic drugs, and reduce tumor growth and metastasis. Therefore, CXCR4 is considered as a target for therapeutic intervention of lung [115],[116] and breast cancer.[117],[118] It has also been used for noninvasive monitoring of disease progression and therapeutic guidance.[114]

 Stemness-Related Pathways

Stem-cell maintenance, self-renewal, and differentiation pathways are involved in embryonic development and adult tissue homeostasis. Cancers commonly display aberrant activities within these pathways, often in a cell-context-dependent manner. Here, we discuss current evidence for Hedgehog (HH), Notch, JAK/STAT, phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and Wnt/β-catenin pathway regulation in CSCs.

Hedgehog pathway

The HH pathway is a major regulator in vertebrate embryonic development, playing critical roles in stem-cell maintenance, cell differentiation, tissue polarity, and cell proliferation, as well as EMT.[119] HH ligands (Desert HH, Sonic HH, and Indian HH) bind to Ptch, activating a cascade of downstream signals that lead to the activation and nuclear localization of TFs, consequently followed by expression of genes that are involved in survival, proliferation, and angiogenesis.[120] HH signaling has been widely implicated in CSC self-renewal and cell fate determination [120] and is considered a potential therapeutic target in breast cancer and pancreatic cancer.[121],[122],[123]

Notch pathway

Notch signaling is a critical part of stem-cell fate determination and angiogenesis. Notch signaling is predominantly involved in cell-cell communication between adjacent cells through transmembrane receptors and ligands. In human ESCs, Notch signaling governs cell fate determination in the developing embryo and is required for undifferentiated ESCs to develop all three embryonic germ layers.[124] In CSCs, it controls tumor immunity and CSC population maintenance.[125],[126] Notch signaling is frequently dysregulated in cancers, providing a survival advantage for tumors. In certain tumor types, activation of Notch signaling aids CSCs in maintaining their population in tumors, inducing EMT, and acquiring chemoresistance.[127] Notch signaling is a potential target for cancers.[128],[129]

JAK/STAT pathway

The JAK-STAT signaling pathway is important in cytokine-mediated immune responses and known to be involved in many biological processes such as proliferation, apoptosis, and migration, as well as the regulation of stem cells. Cancer cells also show frequent dysregulation of the JAK/STAT. Studies in Drosophila first implicated JAK-STAT signaling in the control of stem-cell maintenance in the male germline stem-cell microenvironment.[130],[131] Tightly controlled JAK-STAT signaling is required for stem-cell maintenance and self-renewal. Furthermore, JAK-STAT activity is essential for anchoring the stem cells in their respective niches by regulating different adhesion molecules.

Phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin pathway

The PI3K/Akt and the mTOR signaling pathways are crucial to stem-cell proliferation, metabolism, and differentiation. This pathway is often improperly regulated in human cancers.[132] Over 70% of ovarian cancers have active PI3K/Akt/mTOR pathway, making it a therapeutic target in this cancer type.[133],[134] It is also a therapeutic target for neuroblastoma,[135] endometrial cancer,[136] and acute myeloid leukemia.[137]

Wnt/β-catenin pathway

Pathways induced by Wnt ligands are highly evolutionarily conserved. Given their strong conservation in phylogeny, it is not surprising that Wnt pathways also play key roles in regulating stem-cell differentiation and pluripotency. Consistently in many tissue types, dysregulation of Wnt pathway has been strongly associated with expansion of stem and/or progenitor cell lineages, as well as carcinogenesis.[138] Hence, therapies targeting Wnt pathway may lead to treatment options in hematological malignancies,[139] liver cancer,[140] and other type of tumors.[141]


A primary goal of cancer research is to identify mechanisms driving drug resistance, and recent studies have implicated CSCs in intrinsic resistance models. Similar to normal stem cells, the abilities of self-renewal, maintenance, and differentiation of CSCs make it serve as a core reservoir for cancer initiation, development, and growth. The overexpression of stem-cell-specific TFs may contribute to the pathologic self-renewal characteristics of CSCs while the surface molecules mediate interactions between cells and their microenvironment. Other stemness-related markers and pathways may promote cancer cell proliferation, progression, and metastasis. Our summary of stem cell markers by tissue types and cellular locations in [Table 2] and [Figure 1] highlights the complex nature of CSC regulation, which appears to utilize different pathways in different cell or tissue types. This context dependency makes it hard to find overarching CSC pathways and makers. Understanding the stemness-related features in cancers will not only provide important knowledge on molecular mechanisms for cancer pathogenesis but also shed new light on the development of effective therapeutic approaches, specifically targeting these stemness-related features.{Figure 1}

Financial support and sponsorship

This work was supported in part by NIH Grant (R01CA193520-01A1) and the Jarislowsky Foundation.

Conflicts of interest

There are no conflicts of interest.


1Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003; 3 (12): 895–902.
2Medema JP. Cancer stem cells: the challenges ahead. Nat Cell Biol 2013; 15 (4): 338–44.
3Pattabiraman DR, Weinberg RA. Tackling the cancer stem cells – What challenges do they pose? Nat Rev Drug Discov 2014; 13 (7): 497–512.
4Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suvà ML, Regev A, Bernstein BE. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014; 344 (6190): 1396–401.
5Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126 (4): 663–76.
6Radzisheuskaya A, Silva JC. Do all roads lead to Oct4? The emerging concepts of induced pluripotency. Trends Cell Biol 2014; 24 (5): 275–84.
7Zhu S, Li W, Zhou H, Wei W, Ambasudhan R, Lin T, Kim J, Zhang K, Ding S. Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 2010; 7 (6): 651–5.
8Chen G, Gulbranson DR, Hou Z, Bolin JM, Ruotti V, Probasco MD, Smuga-Otto K, Howden SE, Diol NR, Propson NE, Wagner R, Lee GO, Antosiewicz-Bourget J, Teng JM, Thomson JA. Chemically defined conditions for human iPSC derivation and culture. Nat Methods 2011; 8 (5): 424–9.
9Kelaini S, Cochrane A, Margariti A. Direct reprogramming of adult cells: avoiding the pluripotent state. Stem Cells Cloning 2014; 7: 19–29.
10Monk M, Holding C. Human embryonic genes re-expressed in cancer cells. Oncogene 2001; 20 (56): 8085–91.
11Zhao W, Ji X, Zhang F, Li L, Ma L. Embryonic stem cell markers. Molecules 2012; 17 (6): 6196–236.
12Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J, Klein B. Embryonic stem cell markers expression in cancers. Biochem Biophys Res Commun 2009; 383 (2): 157–62.
13Xu K, Zhu Z, Zeng F. Expression and significance of Oct4 in bladder cancer. J Huazhong Univ Sci Technolog Med Sci 2007; 27 (6): 675–7.
14Hatefi N, Nouraee N, Parvin M, Ziaee SA, Mowla SJ. Evaluating the expression of oct4 as a prognostic tumor marker in bladder cancer. Iran J Basic Med Sci 2012; 15 (6): 1154–61.
15de Resende MF, Chinen LT, Vieira S, Jampietro J, da Fonseca FP, Vassallo J, Campos LC, Guimarães GC, Soares FA, Rocha RM. Prognostication of OCT4 isoform expression in prostate cancer. Tumour Biol 2013; 34 (5): 2665–73.
16Rodini CO, Suzuki DE, Saba-Silva N, Cappellano A, de Souza JE, Cavalheiro S, Toledo SR, Okamoto OK. Expression analysis of stem cell-related genes reveal OCT4 as a predictor of poor clinical outcome in medulloblastoma. J Neurooncol 2012; 106 (1): 71–9.
17Li C, Yan Y, Ji W, Bao L, Qian H, Chen L, Wu M, Chen H, Li Z, Su C. OCT4 positively regulates survivin expression to promote cancer cell proliferation and leads to poor prognosis in esophageal squamous cell carcinoma. PLoS One 2012; 7 (11): e49693.
18Gillis AJ, Stoop H, Biermann K, van Gurp RJ, Swartzman E, Cribbes S, Ferlinz A, Shannon M, Oosterhuis JW, Looijenga LH. Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis. Int J Androl 2011; 34 (4 Pt 2): e160–74.
19Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Hernandez-Garcia S, Elorriaga K, Pandiella A, Rezola R, Martin AG. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene 2012; 31 (11): 1354–65.
20Wang Q, He W, Lu C, Wang Z, Wang J, Giercksky KE, Nesland JM, Suo Z. Oct3/4 and Sox2 are significantly associated with an unfavorable clinical outcome in human esophageal squamous cell carcinoma. Anticancer Res 2009; 29 (4): 1233–41.
21Forghanifard MM, Ardalan Khales S, Javdani-Mallak A, Rad A, Farshchian M, Abbaszadegan MR. Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma. Med Oncol 2014; 31 (4): 922.
22Li XL, Eishi Y, Bai YQ, Sakai H, Akiyama Y, Tani M, Takizawa T, Koike M, Yuasa Y. Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma. Int J Oncol 2004; 24 (2): 257–63.
23Zhang X, Yu H, Yang Y, Zhu R, Bai J, Peng Z, He Y, Chen L, Chen W, Fang D, Bian X, Wang R. SOX2 in gastric carcinoma, but not Hath1, is related to patients' clinicopathological features and prognosis. J Gastrointest Surg 2010; 14 (8): 1220–6.
24Matsuoka J, Yashiro M, Sakurai K, Kubo N, Tanaka H, Muguruma K, Sawada T, Ohira M, Hirakawa K. Role of the stemness factors sox2, oct3/4, and nanog in gastric carcinoma. J Surg Res 2012; 174 (1): 130–5.
25Li X, Wang J, Xu Z, Ahmad A, Li E, Wang Y, Qin S, Wang Q. Expression of Sox2 and Oct4 and their clinical significance in human non-small-cell lung cancer. Int J Mol Sci 2012; 13 (6): 7663–75.
26Chen Y, Huang Y, Huang Y, Chen J, Wang S, Zhou J. The prognostic value of SOX2 expression in non-small cell lung cancer: a meta-analysis. PLoS One 2013; 8 (8): e71140.
27Inoue Y, Matsuura S, Kurabe N, Kahyo T, Mori H, Kawase A, Karayama M, Inui N, Funai K, Shinmura K, Suda T, Sugimura H. Clinicopathological and survival analysis of Japanese patients with resected non-small-cell lung cancer harboring NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, or PIK3CA gene amplification. J Thorac Oncol 2015; 10 (11): 1590–600.
28Sodja E, Rijavec M, Koren A, Sadikov A, Korošec P, Cufer T. The prognostic value of whole blood SOX2, NANOG and OCT4 mRNA expression in advanced small-cell lung cancer. Radiol Oncol 2016; 50 (2): 188–96.
29Ye F, Li Y, Hu Y, Zhou C, Hu Y, Chen H. Expression of Sox2 in human ovarian epithelial carcinoma. J Cancer Res Clin Oncol 2011; 137 (1): 131–7.
30Pham DL, Scheble V, Bareiss P, Fischer A, Beschorner C, Adam A, Bachmann C, Neubauer H, Boesmueller H, Kanz L, Wallwiener D, Fend F, Lengerke C, Perner S, Fehm T, Staebler A. SOX2 expression and prognostic significance in ovarian carcinoma. Int J Gynecol Pathol 2013; 32 (4): 358–67.
31Patel NV, Ghaleb AM, Nandan MO, Yang VW. Expression of the tumor suppressor Kruppel-like factor 4 as a prognostic predictor for colon cancer. Cancer Epidemiol Biomarkers Prev 2010; 19 (10): 2631–8.
32Tai SK, Yang MH, Chang SY, Chang YC, Li WY, Tsai TL, Wang YF, Chu PY, Hsieh SL. Persistent Kruppel-like factor 4 expression predicts progression and poor prognosis of head and neck squamous cell carcinoma. Cancer Sci 2011; 102 (4): 895–902.
33Pandya AY, Talley LI, Frost AR, Fitzgerald TJ, Trivedi V, Chakravarthy M, Chhieng DC, Grizzle WE, Engler JA, Krontiras H, Bland KI, LoBuglio AF, Lobo-Ruppert SM, Ruppert JM. Nuclear localization of KLF4 is associated with an aggressive phenotype in early-stage breast cancer. Clin Cancer Res 2004; 10 (8): 2709–19.
34Liu Z, Yang H, Luo W, Jiang Q, Mai C, Chen Y, Zhen Y, Yu X, Long X, Fang W. Loss of cytoplasmic KLF4 expression is correlated with the progression and poor prognosis of nasopharyngeal carcinoma. Histopathology 2013; 63 (3): 362–70.
35Wang F, Guo Y, Chen Q, Yang Z, Ning N, Zhang Y, Xu Y, Xu X, Tong C, Chai L, Cui W. Stem cell factor SALL4, a potential prognostic marker for myelodysplastic syndromes. J Hematol Oncol 2013; 6 (1): 73.
36Kim J, Orkin SH. Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine. Genome Med 2011; 3 (11): 75.
37Dang CV. MYC on the path to cancer. Cell 2012; 149 (1): 22–35.
38Wang Y, Wu MC, Sham JS, Zhang W, Wu WQ, Guan XY. Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer 2002; 95 (11): 2346–52.
39Riou G, Barrois M, Lê MG, George M, Le Doussal V, Haie C. C-myc proto-oncogene expression and prognosis in early carcinoma of the uterine cervix. Lancet 1987; 1 (8536): 761–3.
40Hart AH, Hartley L, Parker K, Ibrahim M, Looijenga LH, Pauchnik M, Chow CW, Robb L. The pluripotency homeobox gene NANOG is expressed in human germ cell tumors. Cancer 2005; 104 (10): 2092–8.
41Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133 (4): 704–15.
42Bareiss PM, Paczulla A, Wang H, Schairer R, Wiehr S, Kohlhofer U, Rothfuss OC, Fischer A, Perner S, Staebler A, Wallwiener D, Fend F, Fehm T, Pichler B, Kanz L, Quintanilla-Martinez L, Schulze-Osthoff K, Essmann F, Lengerke C. SOX2 expression associates with stem cell state in human ovarian carcinoma. Cancer Res 2013; 73 (17): 5544–55.
43Meng HM, Zheng P, Wang XY, Liu C, Sui HM, Wu SJ, Zhou J, Ding YQ, Li J. Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther 2010; 9 (4): 295–302.
44Xu F, Dai C, Zhang R, Zhao Y, Peng S, Jia C. Nanog: a potential biomarker for liver metastasis of colorectal cancer. Dig Dis Sci 2012; 57 (9): 2340–6.
45Lin T, Ding YQ, Li JM. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol 2012; 29 (2): 878–85.
46Gialmanidis IP, Bravou V, Petrou I, Kourea H, Mathioudakis A, Lilis I, Papadaki H. Expression of Bmi1, FoxF1, Nanog, and gamma-catenin in relation to hedgehog signaling pathway in human non-small-cell lung cancer. Lung 2013; 191 (5): 511–21.
47Li XQ, Yang XL, Zhang G, Wu SP, Deng XB, Xiao SJ, Liu QZ, Yao KT, Xiao GH. Nuclear beta-catenin accumulation is associated with increased expression of Nanog protein and predicts poor prognosis of non-small cell lung cancer. J Transl Med 2013; 11: 114.
48Lee M, Nam EJ, Kim SW, Kim S, Kim JH, Kim YT. Prognostic impact of the cancer stem cell-related marker NANOG in ovarian serous carcinoma. Int J Gynecol Cancer 2012; 22 (9): 1489–96.
49Wang F, Zhao W, Kong N, Cui W, Chai L. The next new target in leukemia: the embryonic stem cell gene SALL4. Mol Cell Oncol 2014; 1 (4): e969169.
50Oikawa T, Kamiya A, Zeniya M, Chikada H, Hyuck AD, Yamazaki Y, Wauthier E, Tajiri H, Miller LD, Wang XW, Reid LM, Nakauchi H. Sal-like protein 4 (SALL4), a stem cell biomarker in liver cancers. Hepatology 2013; 57 (4): 1469–83.
51Masuda S, Suzuki K, Izpisua Belmonte JC. Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. N Engl J Med 2013; 369 (12): 1171–2.
52Zhang L, Yan Y, Jiang Y, Cui Y, Zou Y, Qian J, Luo C, Lu Y, Wu X. The expression of SALL4 in patients with gliomas: high level of SALL4 expression is correlated with poor outcome. J Neurooncol 2015; 121 (2): 261–8.
53Chen CJ, Hsu LS, Lin SH, Chen MK, Wang HK, Hsu JD, Lee H, Yeh KT. Loss of nuclear expression of Kruppel-like factor 4 is associated with poor prognosis in patients with oral cancer. Hum Pathol 2012; 43 (7): 1119–25.
54Sun C, Sun L, Jiang K, Gao DM, Kang XN, Wang C, Zhang S, Huang S, Qin X, Li Y, Liu YK. NANOG promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL/SMAD3 signaling pathway. Int J Biochem Cell Biol 2013; 45 (6): 1099–108.
55Chen Q, Qian J, Lin J, Yang J, Li Y, Wang CZ, Chai HY, Chen XX, Qian Z, Ma JC, Zhang M. Expression of SALL4 gene in patients with acute and chronic myeloid leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2013; 21 (2): 315–9. (in Chinese)
56Colombo N, Carinelli S, Colombo A, Marini C, Rollo D, Sessa C; ESMO Guidelines Working Group. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 23 Suppl 7: vii27–32.
57Basakran NS. CD44 as a potential diagnostic tumor marker. Saudi Med J 2015; 36 (3): 273–9.
58Joshua B, Kaplan MJ, Doweck I, Pai R, Weissman IL, Prince ME, Ailles LE. Frequency of cells expressing CD44, a head and neck cancer stem cell marker: correlation with tumor aggressiveness. Head Neck 2012; 34 (1): 42–9.
59Palapattu GS, Wu C, Silvers CR, Martin HB, Williams K, Salamone L, Bushnell T, Huang LS, Yang Q, Huang J. Selective expression of CD44, a putative prostate cancer stem cell marker, in neuroendocrine tumor cells of human prostate cancer. Prostate 2009; 69 (7): 787–98.
60Orian-Rousseau V. CD44, a therapeutic target for metastasising tumours. Eur J Cancer 2010; 46 (7): 1271–7.
61Arabi L, Badiee A, Mosaffa F, Jaafari MR. Targeting CD44 expressing cancer cells with anti-CD44 monoclonal antibody improves cellular uptake and antitumor efficacy of liposomal doxorubicin. J Control Release 2015; 220(Pt A): 275–86.
62Zhang S, Wu CC, Fecteau JF, Cui B, Chen L, Zhang L, Wu R, Rassenti L, Lao F, Weigand S, Kipps TJ. Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44. Proc Natl Acad Sci U S A 2013; 110 (15): 6127–32.
63Handgretinger R, Gordon PR, Leimig T, Chen X, Buhring HJ, Niethammer D, Kuci S. Biology and plasticity of CD133+ hematopoietic stem cells. Ann N Y Acad Sci 2003; 996: 141–51.
64Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63 (18): 5821–8.
65Li Z. CD133: a stem cell biomarker and beyond. Exp Hematol Oncol 2013; 2 (1): 17.
66Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature 2004; 432 (7015): 396–401.
67Catalano V, Di Franco S, Iovino F, Dieli F, Stassi G, Todaro M. CD133 as a target for colon cancer. Expert Opin Ther Targets 2012; 16 (3): 259–67.
68Skubitz AP, Taras EP, Boylan KL, Waldron NN, Oh S, Panoskaltsis-Mortari A, Vallera DA. Targeting CD133 in an in vivo ovarian cancer model reduces ovarian cancer progression. Gynecol Oncol 2013; 130 (3): 579–87.
69Rappa G, Fodstad O, Lorico A. The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. Stem Cells 2008; 26 (12): 3008–17.
70Smith LM, Nesterova A, Ryan MC, Duniho S, Jonas M, Anderson M, Zabinski RF, Sutherland MK, Gerber HP, Van Orden KL, Moore PA, Ruben SM, Carter PJ. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer 2008; 99 (1): 100–9.
71Mao XG, Zhang X, Xue XY, Guo G, Wang P, Zhang W, Fei Z, Zhen HN, You SW, Yang H. Brain tumor stem-like cells identified by neural stem cell marker CD15. Transl Oncol 2009; 2 (4): 247–57.
72Lin W, Modiano JF, Ito D. Stage-specific embryonic antigen (SSEA): determining the expression in canine glioblastoma, melanoma, and mammary cancer cells. J Vet Sci 2017; 18 (1): 101–4.
73Giwercman A, Andrews PW, Jørgensen N, Müller J, Graem N, Skakkebaek NE. Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis. Cancer 1993; 72 (4): 1308–14.
74Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007; 449 (7165): 1003–7.
75Simon E, Petke D, Böger C, Behrens HM, Warneke V, Ebert M, Röcken C. The spatial distribution of LGR5+ cells correlates with gastric cancer progression. PLoS One 2012; 7 (4): e35486.
76He J, Liu Y, Zhu T, Zhu J, Dimeco F, Vescovi AL, Heth JA, Muraszko KM, Fan X, Lubman DM. CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays. Mol Cell Proteomics 2012; 11 (6): M111.010744.
77Parry PV, Engh JA. CD90 is identified as a marker for cancer stem cells in high-grade gliomas using tissue microarrays. Neurosurgery 2012; 70 (4): N23–4.
78Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PW, Lam CT, Poon RT, Fan ST. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 2008; 13 (2): 153–66.
79Kawamura K, Hiroshima K, Suzuki T, Chai K, Yamaguchi N, Shingyoji M, Yusa T, Tada Y, Takiguchi Y, Tatsumi K, Shimada H, Tagawa M. CD90 is a diagnostic marker to differentiate between malignant pleural mesothelioma and lung carcinoma with immunohistochemistry. Am J Clin Pathol 2013; 140 (4): 544–9.
80Yan X, Luo H, Zhou X, Zhu B, Wang Y, Bian X. Identification of CD90 as a marker for lung cancer stem cells in A549 and H446 cell lines. Oncol Rep 2013; 30 (6): 2733–40.
81Auewarakul CU, Lauhakirti D, Promsuwicha O, Munkhetvit C. C-kit receptor tyrosine kinase (CD117) expression and its positive predictive value for the diagnosis of Thai adult acute myeloid leukemia. Ann Hematol 2006; 85 (2): 108–12.
82Eren R, Aslan C, Yokuş O, Doǧu MH, Suyani E. T-cell acute lymphoblastic leukemia with co-expression of CD56, CD34, CD117 and CD33: A case with poor prognosis. Mol Clin Oncol 2016; 5 (2): 331–2.
83Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M. CD117: A sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 1998; 11 (8): 728–34.
84Barth PJ, Schenck zu Schweinsberg T, Ramaswamy A, Moll R. CD34+ fibrocytes, alpha-smooth muscle antigen-positive myofibroblasts, and CD117 expression in the stroma of invasive squamous cell carcinomas of the oral cavity, pharynx, and larynx. Virchows Arch 2004; 444 (3): 231–4.
85Mărgăritescu C, Pirici D, Simionescu C, Stepan A. The utility of CD44, CD117 and CD133 in identification of cancer stem cells (CSC) in oral squamous cell carcinomas (OSCC). Rom J Morphol Embryol 2011; 52(3 Suppl): 985–93.
86Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 2008; 68 (11): 4311–20.
87Luo L, Zeng J, Liang B, Zhao Z, Sun L, Cao D, Yang J, Shen K. Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol 2011; 91 (2): 596–602.
88Becker G, Schmitt-Graeff A, Ertelt V, Blum HE, Allgaier HP. CD117 (c-kit) expression in human hepatocellular carcinoma. Clin Oncol (R Coll Radiol) 2007; 19 (3): 204–8.
89Potti A, Ganti AK, Tendulkar K, Chitajallu S, Sholes K, Koch M, Kargas S. HER-2/neu and CD117 (C-kit) overexpression in hepatocellular and pancreatic carcinoma. Anticancer Res 2003; 23 (3B): 2671–4.
90Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R Jr., Badve S, Nakshatri H. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 2006; 8 (5): R59.
91Giatromanolaki A, Sivridis E, Fiska A, Koukourakis MI. The CD44+/CD24- phenotype relates to 'triple-negative' state and unfavorable prognosis in breast cancer patients. Med Oncol 2011; 28 (3): 745–52.
92Adamczyk A, Niemiec JA, Ambicka A, Mucha-Małecka A, Mituś J, Ryś J. CD44/CD24 as potential prognostic markers in node-positive invasive ductal breast cancer patients treated with adjuvant chemotherapy. J Mol Histol 2014; 45 (1): 35–45.
93Lee HJ, Choe G, Jheon S, Sung SW, Lee CT, Chung JH. CD24, a novel cancer biomarker, predicting disease-free survival of non-small cell lung carcinomas: a retrospective study of prognostic factor analysis from the viewpoint of forthcoming (seventh) new TNM classification. J Thorac Oncol 2010; 5 (5): 649–57.
94Karimi-Busheri F, Rasouli-Nia A, Zadorozhny V, Fakhrai H. CD24+/CD38- as new prognostic marker for non-small cell lung cancer. Multidiscip Respir Med 2013; 8 (1): 65.
95Kristiansen G, Denkert C, Schlüns K, Dahl E, Pilarsky C, Hauptmann S. CD24 is expressed in ovarian cancer and is a new independent prognostic marker of patient survival. Am J Pathol 2002; 161 (4): 1215–21.
96Qian X, Wagner S, Ma C, Coordes A, Gekeler J, Klussmann JP, Hummel M, Kaufmann AM, Albers AE. Prognostic significance of ALDH1A1-positive cancer stem cells in patients with locally advanced, metastasized head and neck squamous cell carcinoma. J Cancer Res Clin Oncol 2014; 140 (7): 1151–8.
97Yang L, Ren Y, Yu X, Qian F, Bian BS, Xiao HL, Wang WG, Xu SL, Yang J, Cui W, Liu Q, Wang Z, Guo W, Xiong G, Yang K, Qian C, Zhang X, Zhang P, Cui YH, Bian XW. ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma. Mod Pathol 2014; 27 (5): 775–83.
98Li H, Bitler BG, Vathipadiekal V, Maradeo ME, Slifker M, Creasy CL, Tummino PJ, Cairns P, Birrer MJ, Zhang R. ALDH1A1 is a novel EZH2 target gene in epithelial ovarian cancer identified by genome-wide approaches. Cancer Prev Res (Phila) 2012; 5 (3): 484–91.
99Condello S, Morgan CA, Nagdas S, Cao L, Turek J, Hurley TD, Matei D. beta-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids. Oncogene 2015; 34 (18): 2297–308.
100Liu X, Wang L, Cui W, Yuan X, Lin L, Cao Q, Wang N, Li Y, Guo W, Zhang X, Wu C, Yang J. Targeting ALDH1A1 by disulfiram/copper complex inhibits non-small cell lung cancer recurrence driven by ALDH-positive cancer stem cells. Oncotarget 2016; 7 (36): 58516–30.
101Gong H, Zhang YC, Liu WL. Regulatory effects of Bmi-1 gene on self-renewal of hematopoietic stem cells-review. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006; 14 (2): 413–5. (in Chinese)
102Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 2003; 425 (6961): 962–7.
103Nör C, Zhang Z, Warner KA, Bernardi L, Visioli F, Helman JI, Roesler R, Nör JE. Cisplatin induces Bmi-1 and enhances the stem cell fraction in head and neck cancer. Neoplasia 2014; 16 (2): 137–46.
104Häyry V, Tynninen O, Haapasalo HK, Wölfer J, Paulus W, Hasselblatt M, Sariola H, Paetau A, Sarna S, Niemelä M, Wartiovaara K, Nupponen NN. Stem cell protein BMI-1 is an independent marker for poor prognosis in oligodendroglial tumours. Neuropathol Appl Neurobiol 2008; 34 (5): 555–63.
105Arnes JB, Collett K, Akslen LA. Independent prognostic value of the basal-like phenotype of breast cancer and associations with EGFR and candidate stem cell marker BMI-1. Histopathology 2008; 52 (3): 370–80.
106Wang Y, Zhe H, Ding Z, Gao P, Zhang N, Li G. Cancer stem cell marker Bmi-1 expression is associated with basal-like phenotype and poor survival in breast cancer. World J Surg 2012; 36 (5): 1189–94.
107Strojnik T, Røsland GV, Sakariassen PO, Kavalar R, Lah T. Neural stem cell markers, nestin and musashi proteins, in the progression of human glioma: correlation of nestin with prognosis of patient survival. Surg Neurol 2007; 68 (2): 133–43.
108Neradil J, Veselska R. Nestin as a marker of cancer stem cells. Cancer Sci 2015; 106 (7): 803–11.
109Wang H, Wang S, Hu J, Kong Y, Chen S, Li L, Li L. Oct4 is expressed in Nestin-positive cells as a marker for pancreatic endocrine progenitor. Histochem Cell Biol 2009; 131 (5): 553–63.
110Yamahatsu K, Matsuda Y, Ishiwata T, Uchida E, Naito Z. Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis. Int J Oncol 2012; 40 (5): 1345–57.
111Matsuda Y, Hagio M, Ishiwata T. Nestin: a novel angiogenesis marker and possible target for tumor angiogenesis. World J Gastroenterol 2013; 19 (1): 42–8.
112Matsuda Y, Hagio M, Ishiwata T. Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer. Oncotarget 2013; 4 (5): 739–50.
113Liekens S, Schols D, Hatse S. CXCL12-CXCR4 axis in angiogenesis, metastasis and stem cell mobilization. Curr Pharm Des 2010; 16 (35): 3903–20.
114Chatterjee S, Behnam Azad B, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res 2014; 124: 31–82.
115Otsuka S, Bebb G. The CXCR4/SDF-1 chemokine receptor axis: a new target therapeutic for non-small cell lung cancer. J Thorac Oncol 2008; 3 (12): 1379–83.
116Wang Z, Sun J, Feng Y, Tian X, Wang B, Zhou Y. Oncogenic roles and drug target of CXCR4/CXCL12 axis in lung cancer and cancer stem cell. Tumour Biol 2016; 37 (7): 8515–28.
117Epstein RJ. The CXCL12-CXCR4 chemotactic pathway as a target of adjuvant breast cancer therapies. Nat Rev Cancer 2004; 4 (11): 901–9.
118Gil M, Seshadri M, Komorowski MP, Abrams SI, Kozbor D. Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases. Proc Natl Acad Sci U S A 2013; 110 (14): E1291–300.
119Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008; 22 (18): 2454–72.
120Cochrane CR, Szczepny A, Watkins DN, Cain JE. Hedgehog signaling in the maintenance of cancer stem cells. Cancers (Basel) 2015; 7 (3): 1554–85.
121Merchant AA, Matsui W. Targeting Hedgehog – A cancer stem cell pathway. Clin Cancer Res 2010; 16 (12): 3130–40.
122Gould A, Missailidis S. Targeting the hedgehog pathway: the development of cyclopamine and the development of anti-cancer drugs targeting the hedgehog pathway. Mini Rev Med Chem 2011; 11 (3): 200–13.
123Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, Yang SX, Ivy SP. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 2015; 12 (8): 445–64.
124Yu X, Zou J, Ye Z, Hammond H, Chen G, Tokunaga A, Mali P, Li YM, Civin C, Gaiano N, Cheng L. Notch signaling activation in human embryonic stem cells is required for embryonic, but not trophoblastic, lineage commitment. Cell Stem Cell 2008; 2 (5): 461–71.
125Hassan KA, Wang L, Korkaya H, Chen G, Maillard I, Beer DG, Kalemkerian GP, Wicha MS. Notch pathway activity identifies cells with cancer stem cell-like properties and correlates with worse survival in lung adenocarcinoma. Clin Cancer Res 2013; 19 (8): 1972–80.
126Abel EV, Kim EJ, Wu J, Hynes M, Bednar F, Proctor E, Wang L, Dziubinski ML, Simeone DM. The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer. PLoS One 2014; 9 (3): e91983.
127Capaccione KM, Pine SR. The Notch signaling pathway as a mediator of tumor survival. Carcinogenesis 2013; 34 (7): 1420–30.
128Hirose H, Ishii H, Mimori K, Ohta D, Ohkuma M, Tsujii H, Saito T, Sekimoto M, Doki Y, Mori M. Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors. Oncol Rep 2010; 23 (1): 35–43.
129Yuan X, Wu H, Xu H, Xiong H, Chu Q, Yu S, Wu GS, Wu K. Notch signaling: an emerging therapeutic target for cancer treatment. Cancer Lett 2015; 369 (1): 20–7.
130Bausek N. JAK-STAT signaling in stem cells and their niches in Drosophila. JAKSTAT 2013; 2 (3): e25686.
131Stine RR, Matunis EL. JAK-STAT signaling in stem cells. Adv Exp Med Biol 2013; 786: 247–67.
132Morgensztern D, McLeod HL. PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs 2005; 16 (8): 797–803.
133Li H, Zeng J, Shen K. PI3K/AKT/mTOR signaling pathway as a therapeutic target for ovarian cancer. Arch Gynecol Obstet 2014; 290 (6): 1067–78.
134Mabuchi S, Kuroda H, Takahashi R, Sasano T. The PI3K/AKT/mTOR pathway as a therapeutic target in ovarian cancer. Gynecol Oncol 2015; 137 (1): 173–9.
135Fulda S. The PI3K/Akt/mTOR pathway as therapeutic target in neuroblastoma. Curr Cancer Drug Targets 2009; 9 (6): 729–37.
136Slomovitz BM, Coleman RL. The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res 2012; 18 (21): 5856–64.
137Dos Santos C, Récher C, Demur C, Payrastre B. The PI3K/Akt/mTOR pathway: a new therapeutic target in the treatment of acute myeloid leukemia. Bull Cancer 2006; 93 (5): 445–7.
138Valkenburg KC, Graveel CR, Zylstra-Diegel CR, Zhong Z, Williams BO. Wnt/beta-catenin signaling in normal and cancer stem cells. Cancers (Basel) 2011; 3 (2): 2050–79.
139Ashihara E, Takada T, Maekawa T. Targeting the canonical Wnt/beta-catenin pathway in hematological malignancies. Cancer Sci 2015; 106 (6): 665–71.
140Gedaly R, Galuppo R, Daily MF, Shah M, Maynard E, Chen C, Zhang X, Esser KA, Cohen DA, Evers BM, Jiang J, Spear BT. Targeting the Wnt/beta-catenin signaling pathway in liver cancer stem cells and hepatocellular carcinoma cell lines with FH535. PLoS One 2014; 9 (6): e99272.
141Yao H, Ashihara E, Maekawa T. Targeting the Wnt/beta-catenin signaling pathway in human cancers. Expert Opin Ther Targets 2011; 15 (7): 873–87.