Epithelial-to-mesenchymal transition and cancer stem(-like) cells in head and neck squamous cell carcinoma

Cancer Letters

Volumn 338, Issue 1, 2013, Pages 47-56

  Chen, Chao ^a,b   Zimmermann, Miriam ^c   Tinhofer, Inge ^b   Kaufmann, Andreas M ^b   Albers, Andreas E ^b  

^a ZHEJIANG CANCER HOSPITAL   (China)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

Cancer stem( like) cells; Epithelial to mesenchymal transition; HNSCC; Metastasis; MicroRNA; Therapeutic target regulation

Indexed keywords

GEFITINIB; MATRIX METALLOPROTEINASE INHIBITOR; MICRORNA; MICRORNA 107; PROANTHOCYANIDIN; SALINOMYCIN; TRICHOSTATIN A; UVOMORULIN; VIMENTIN; VORINOSTAT;

CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER STEM CELL; CANCER SURVIVAL; CANCER THERAPY; CELL FUNCTION; CELL MIGRATION; CELL RENEWAL; CIRCULATING TUMOR CELL; DRUG MECHANISM; EPITHELIAL MESENCHYMAL TRANSITION; GENE EXPRESSION REGULATION; GENETIC RISK; HEAD AND NECK CARCINOMA; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; METASTASIS; OVERALL SURVIVAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; SHORT SURVEY; TARGET CELL; TUMOR INVASION;

EID: 84882924026     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2012.06.013     Document Type: Review

References (194)

1. Greenlee R.T., Hill-Harmon M.B., Murray T., Thun M. Cancer statistics. CA Cancer J. Clin. 2001, 51(2001):15-36.
2. Jones A.S., Morar P., Phillips D.E., Field J.K., Husband D., Helliwell T.R. Second primary tumors in patients with head and neck squamous cell carcinoma. Cancer 1995, 75:1343-1353.
3. Leemans C.R., Tiwari R., Nauta J.J., van der Waal I., Snow G.B. Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. Cancer 1994, 73:187-190.
4. Pignon J.P., Baujat B., Bourhis J. Individual patient data meta-analyses in head and neck carcinoma: what have we learnt?. Cancer Radiother. 2005, 9:31-36.
5. Thiery J.P. Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2002, 2:442-454.
6. Brabletz T., Jung A., Reu S., Porzner M., Hlubek F., Kunz-Schughart L.A., Knuechel R., Kirchner T. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc. Natl. Acad. Sci. USA 2001, 98:10356-10361.
7. Brabletz T., Jung A., Spaderna S., Hlubek F., Kirchner T. Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat. Rev. Cancer 2005, 5:744-749.
8. Lee J.M., Dedhar S., Kalluri R., Thompson E.W. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J. Cell Biol. 2006, 172:973-981.
9. Radisky D.C., LaBarge M.A. Epithelial-mesenchymal transition and the stem cell phenotype. Cell Stem Cell 2008, 2:511-512.
10. Hollier B.G., Evans K., Mani S.A. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J. Mammary Gland Biol. Neoplasia 2009, 14:29-43.
11. Hugo H., Ackland M.L., Blick T., Lawrence M.G., Clements J.A., Williams E.D., Thompson E.W. Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J. Cell. Physiol. 2007, 213:374-383.
12. Moustakas A., Heldin C.H. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007, 98:1512-1520.
13. Jouppila-Matto A., Narkio-Makela M., Soini Y., Pukkila M., Sironen R., Tuhkanen H., Mannermaa A., Kosma V.M. Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression. BMC Cancer 2011, 11:350.
14. Yu L., Lu S., Tian J., Ma J., Li J., Wang H., Xu W. TWIST expression in hypopharyngeal cancer and the mechanism of TWIST-induced promotion of metastasis. Oncol. Rep. 2012, 27:416-422.
15. Mandal M., Myers J.N., Lippman S.M., Johnson F.M., Williams M.D., Rayala S., Ohshiro K., Rosenthal D.I., Weber R.S., Gallick G.E., El-Naggar A.K. Epithelial to mesenchymal transition in head and neck squamous carcinoma: association of Src activation with E-cadherin down-regulation, vimentin expression, and aggressive tumor features. Cancer 2008, 112:2088-2100.
16. Nijkamp M.M., Span P.N., Hoogsteen I.J., van der Kogel A.J., Kaanders J.H., Bussink J. Expression of E-cadherin and vimentin correlates with metastasis formation in head and neck squamous cell carcinoma patients. Radiother. Oncol. 2011, 99:344-348.
17. Chen C., Wei Y., Hummel M., Hoffmann T.K., Gross M., Kaufmann A.M., Albers A.E. Evidence for epithelial-mesenchymal transition in cancer stem cells of head and neck squamous cell carcinoma. PLoS One 2011, 6:e16466.
18. Rogers S.J., Harrington K.J., Rhys-Evans P., O-Charoenrat P., Eccles S.A. Biological significance of c-erbB family oncogenes in head and neck cancer. Cancer Metastasis Rev. 2005, 24:47-69.
19. Ang K.K., Berkey B.A., Tu X., Zhang H.Z., Katz R., Hammond E.H., Fu K.K., Milas L. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002, 62:7350-7356.
20. Rubin Grandis J., Melhem M.F., Gooding W.E., Day R., Holst V.A., Wagener M.M., Drenning S.D., Tweardy D.J. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J. Natl. Cancer Inst. 1998, 90:824-832.
21. Box C., Rogers S.J., Mendiola M., Eccles S.A. Tumour-microenvironmental interactions: paths to progression and targets for treatment. Semin. Cancer Biol. 2010, 20:128-138.
22. Zuo J.H., Zhu W., Li M.Y., Li X.H., Yi H., Zeng G.Q., Wan X.X., He Q.Y., Li J.H., Qu J.Q., Chen Y., Xiao Z.Q. Activation of EGFR promotes squamous carcinoma SCC10A cell migration and invasion via inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin. J. Cell. Biochem. 2011, 112:2508-2517.
23. Holz C., Niehr F., Boyko M., Hristozova T., Distel L., Budach V., Tinhofer I. Epithelial-mesenchymal-transition induced by EGFR activation interferes with cell migration and response to irradiation and cetuximab in head and neck cancer cells. Radiother. Oncol. 2011, 101:158-164.
24. Bourguignon L.Y., Gilad E., Brightman A., Diedrich F., Singleton P. Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+ signaling, and cytoskeleton modification in head and neck squamous cell carcinoma cells. J. Biol. Chem. 2006, 281:14026-14040.
25. Wang S.J., Bourguignon L.Y. Hyaluronan and the interaction between CD44 and epidermal growth factor receptor in oncogenic signaling and chemotherapy resistance in head and neck cancer. Arch. Otolaryngol. Head Neck Surg. 2006, 132:771-778.
26. Otrock Z.K., Mahfouz R.A., Makarem J.A., Shamseddine A.I. Understanding the biology of angiogenesis: review of the most important molecular mechanisms. Blood Cells Mol. Dis. 2007, 39:212-220.
27. Miettinen P.J., Ebner R., Lopez A.R., Derynck R. TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J. Cell Biol. 1994, 127:2021-2036.
28. Araki S., Eitel J.A., Batuello C.N., Bijangi-Vishehsaraei K., Xie X.J., Danielpour D., Pollok K.E., Boothman D.A., Mayo L.D. TGF-beta1-induced expression of human Mdm2 correlates with late-stage metastatic breast cancer. J. Clin. Invest. 2010, 120:290-302.
29. Wikstrom P., Stattin P., Franck-Lissbrant I., Damber J.E., Bergh A. Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer. Prostate 1998, 37:19-29.
30. Takayama S., Hatori M., Kurihara Y., Kinugasa Y., Shirota T., Shintani S. Inhibition of TGF-beta1 suppresses motility and invasiveness of oral squamous cell carcinoma cell lines via modulation of integrins and down-regulation of matrix-metalloproteinases. Oncol. Rep. 2009, 21:205-210.
31. Gordon K.J., Kirkbride K.C., How T., Blobe G.C. Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2. Carcinogenesis 2009, 30:238-248.
32. Xu J., Lamouille S., Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009, 19:156-172.
33. Xu T., Yu C.Y., Sun J.J., Liu Y., Wang X.W., Pi L.M., Tian Y.Q., Zhang X. Bone morphogenetic protein-4-induced epithelial-mesenchymal transition and invasiveness through Smad1-mediated signal pathway in squamous cell carcinoma of the head and neck. Arch. Med. Res. 2011, 42:128-137.
34. Qiao B., Johnson N.W., Chen X., Li R., Tao Q., Gao J. Disclosure of a stem cell phenotype in an oral squamous cell carcinoma cell line induced by BMP-4 via an epithelial-mesenchymal transition. Oncol. Rep. 2011, 26:455-461.
35. Chung C.H., Parker J.S., Ely K., Carter J., Yi Y., Murphy B.A., Ang K.K., El-Naggar A.K., Zanation A.M., Cmelak A.J., Levy S., Slebos R.J., Yarbrough W.G. Gene expression profiles identify epithelial-to-mesenchymal transition and activation of nuclear factor-kappaB signaling as characteristics of a high-risk head and neck squamous cell carcinoma. Cancer Res. 2006, 66:8210-8218.
36. Kupferman M.E., Jiffar T., El-Naggar A., Yilmaz T., Zhou G., Xie T., Feng L., Wang J., Holsinger F.C., Yu D., Myers J.N. TrkB induces EMT and has a key role in invasion of head and neck squamous cell carcinoma. Oncogene 2010, 29:2047-2059.
37. Humtsoe J.O., Koya E., Pham E., Aramoto T., Zuo J., Ishikawa T., Kramer R.H. Transcriptional profiling identifies upregulated genes following induction of epithelial-mesenchymal transition in squamous carcinoma cells. Exp. Cell Res. 2012, 318:379-390.
38. Visvader J.E., Lindeman G.J. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat. Rev. Cancer 2008, 8:755-768.
39. Greaves M. Cancer stem cells: back to Darwin?. Semin. Cancer Biol. 2010, 20:65-70.
40. Bonnet D., Dick J.E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 1997, 3:730-737.
41. Gupta P.B., Chaffer C.L., Weinberg R.A. Cancer stem cells: mirage or reality?. Nat. Med. 2009, 15:1010-1012.
42. Cameron S.R., Dahler A.L., Endo-Munoz L.B., Jabbar I., Thomas G.P., Leo P.J., Poth K., Rickwood D., Guminski A., Saunders N.A. Tumor-initiating activity and tumor morphology of HNSCC is modulated by interactions between clonal variants within the tumor. Lab. Invest. 2010, 90:1594-1603.
43. Umezawa A., Gorham J.D. Dueling models in head and neck tumor formation. Lab. Invest. 2010, 90:1546-1548.
44. Adams J.M., Strasser A. Is tumor growth sustained by rare cancer stem cells or dominant clones?. Cancer Res. 2008, 68:4018-4021.
45. Singh A., Settleman J. EMT, cancer stem cells and drug resistance. an emerging axis of evil in the war on cancer. Oncogene 2010, 29:4741-4751.
46. Soeda A., Park M., Lee D., Mintz A., Androutsellis-Theotokis A., McKay R.D., Engh J., Iwama T., Kunisada T., Kassam A.B., Pollack I.F., Park D.M. Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene 2009, 28:3949-3959.
47. Mani S.A., Guo W., Liao M.J., Eaton E.N., Ayyanan A., Zhou A.Y., Brooks M., Reinhard F., Zhang C.C., Shipitsin M., Campbell L.L., Polyak K., Brisken C., Yang J., Weinberg R.A. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133:704-715.
48. Wang Z., Li Y., Ahmad A., Azmi A.S., Kong D., Banerjee S., Sarkar F.H. Targeting miRNAs involved in cancer stem cell and EMT regulation: an emerging concept in overcoming drug resistance. Drug Resist. Updat. 2010, 13:109-118.
49. Santisteban M., Reiman J.M., Asiedu M.K., Behrens M.D., Nassar A., Kalli K.R., Haluska P., Ingle J.N., Hartmann L.C., Manjili M.H., Radisky D.C., Ferrone S., Knutson K.L. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009, 69:2887-2895.
50. Morel A.P., Lievre M., Thomas C., Hinkal G., Ansieau S., Puisieux A. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008, 3:e2888.
51. Biddle A., Liang X., Gammon L., Fazil B., Harper L.J., Emich H., Costea D.E., Mackenzie I.C. Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res. 2011, 71:5317-5326.
52. Schneider M., Hansen J.L., Sheikh S.P. S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?. J. Mol. Med. (Berlin) 2008, 86:507-522.
53. Cordenonsi M., Zanconato F., Azzolin L., Forcato M., Rosato A., Frasson C., Inui M., Montagner M., Parenti A.R., Poletti A., Daidone M.G., Dupont S., Basso G., Bicciato S., Piccolo S. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 2011, 147:759-772.
54. Chen Y.S., Wu M.J., Huang C.Y., Lin S.C., Chuang T.H., Yu C.C., Lo J.F. CD133/Src axis mediates tumor initiating property and epithelial-mesenchymal transition of head and neck cancer. PLoS One 2011, 6:e28053.
55. Li R., Liang J., Ni S., Zhou T., Qing X., Li H., He W., Chen J., Li F., Zhuang Q., Qin B., Xu J., Li W., Yang J., Gan Y., Qin D., Feng S., Song H., Yang D., Zhang B., Zeng L., Lai L., Esteban M.A., Pei D. A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 2010, 7:51-63.
56. Gibbons D.L., Lin W., Creighton C.J., Rizvi Z.H., Gregory P.A., Goodall G.J., Thilaganathan N., Du L., Zhang Y., Pertsemlidis A., Kurie J.M. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Gene Dev. 2009, 23:2140-2151.
57. Xu Y., Brenn T., Brown E.R., Doherty V., Melton D.W. Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors. Br. J. Cancer 2012, 106:553-561.
58. Peter M.E. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle 2009, 8:843-852.
59. Gregory P.A., Bert A.G., Paterson E.L., Barry S.C., Tsykin A., Farshid G., Vadas M.A., Khew-Goodall Y., Goodall G.J. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat. Cell Biol. 2008, 10:593-601.
60. Kong D., Li Y., Wang Z., Banerjee S., Ahmad A., Kim H.R., Sarkar F.H. MiR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells. Stem Cells 2009, 27:1712-1721.
61. Li Y., VandenBoom T.G., Kong D., Wang Z., Ali S., Philip P.A., Sarkar F.H. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 2009, 69:6704-6712.
62. Babu J.M., Prathibha R., Jijith V.S., Hariharan R., Pillai M.R. A miR-centric view of head and neck cancers. Biochim. Biophys. Acta 1816, 2011:67-72.
63. Lo W.L., Yu C.C., Chiou G.Y., Chen Y.W., Huang P.I., Chien C.S., Tseng L.M., Chu P.Y., Lu K.H., Chang K.W., Kao S.Y., Chiou S.H. MicroRNA-200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells. J. Pathol. 2011, 223:482-495.
64. Bracken C.P., Gregory P.A., Kolesnikoff N., Bert A.G., Wang J., Shannon M.F., Goodall G.J. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 2008, 68:7846-7854.
65. Burk U., Schubert J., Wellner U., Schmalhofer O., Vincan E., Spaderna S., Brabletz T. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008, 9:582-589.
66. Huang Q., Gumireddy K., Schrier M., le Sage C., Nagel R., Nair S., Egan D.A., Li A., Huang G., Klein-Szanto A.J., Gimotty P.A., Katsaros D., Coukos G., Zhang L., Pure E., Agami R. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat. Cell Biol. 2008, 10:202-210.
67. Ma L., Teruya-Feldstein J., Weinberg R.A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007, 449:682-688.
68. Martello G., Rosato A., Ferrari F., Manfrin A., Cordenonsi M., Dupont S., Enzo E., Guzzardo V., Rondina M., Spruce T., Parenti A.R., Daidone M.G., Bicciato S., Piccolo S. A MicroRNA targeting dicer for metastasis control. Cell 2010, 141:1195-1207.
69. J. Datta, A. Smith, J.C. Lang, M. Islam, D. Dutt, T.N. Teknos, Q. Pan, microRNA-107 functions as a candidate tumor-suppressor gene in head and neck squamous cell carcinoma by downregulation of protein kinase Cvarepsilon, Oncogene, 2011. http://dx.doi.org/10.1038/onc.2011.565.
70. Hui A.B., Lenarduzzi M., Krushel T., Waldron L., Pintilie M., Shi W., Perez-Ordonez B., Jurisica I., O'Sullivan B., Waldron J., Gullane P., Cummings B., Liu F.F. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin. Cancer Res. 2010, 16:1129-1139.
71. Kimura S., Naganuma S., Susuki D., Hirono Y., Yamaguchi A., Fujieda S., Sano K., Itoh H. Expression of microRNAs in squamous cell carcinoma of human head and neck and the esophagus: miR-205 and miR-21 are specific markers for HNSCC and ESCC. Oncol. Rep. 2010, 23:1625-1633.
72. Kozaki K., Imoto I., Mogi S., Omura K., Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008, 68:2094-2105.
73. Liu X., Wang C., Chen Z., Jin Y., Wang Y., Kolokythas A., Dai Y., Zhou X. MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines. Biochem. J. 2011, 440:23-31.
74. Tran N., McLean T., Zhang X., Zhao C.J., Thomson J.M., O'Brien C., Rose B. MicroRNA expression profiles in head and neck cancer cell lines. Biochem. Biophys. Res. Commun. 2007, 358:12-17.
75. Wong T.S., Liu X.B., Wong B.Y., Ng R.W., Yuen A.P., Wei W.I. Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin. Cancer Res. 2008, 14:2588-2592.
76. Zavadil J., Narasimhan M., Blumenberg M., Schneider R.J. Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial plasticity. Cells Tissues Organs 2007, 185:157-161.
77. Davis B.N., Hilyard A.C., Lagna G., Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature 2008, 454:56-61.
78. Cottonham C.L., Kaneko S., Xu L. MiR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon carcinoma cells. J. Biol. Chem. 2010, 285:35293-35302.
79. Zhu S., Wu H., Wu F., Nie D., Sheng S., Mo Y.Y. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 2008, 18:350-359.
80. Asangani I.A., Rasheed S.A., Nikolova D.A., Leupold J.H., Colburn N.H., Post S., Allgayer H. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 2008, 27:2128-2136.
81. Han M., Wang Y., Liu M., Bi X., Bao J., Zeng N., Zhu Z., Mo Z., Wu C., Chen X. MiR-21 regulates epithelial-mesenchymal transition phenotype and hypoxia-inducible factor-1alpha expression in third-sphere forming breast cancer stem cell-like cells. Cancer Sci. 2012, 103:1058-1064.
82. Zavadil J., Haley J., Kalluri R., Muthuswamy S.K., Thompson E. Epithelial-mesenchymal transition. Cancer Res. 2008, 68:9574-9577.
83. Bourguignon L.Y., Earle C., Wong G., Spevak C.C., Krueger K. Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells. Oncogene 2012, 31:149-160.
84. Lu Z., Liu M., Stribinskis V., Klinge C.M., Ramos K.S., Colburn N.H., Li Y. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene 2008, 27:4373-4379.
85. Xu X., Chen Z., Zhao X., Wang J., Ding D., Wang Z., Tan F., Tan X., Zhou F., Sun J., Sun N., Gao Y., Shao K., Li N., Qiu B., He J. MicroRNA-25 promotes cell migration and invasion in esophageal squamous cell carcinoma. Biochem. Biophys. Res. Commun. 2012, 421:640-645.
86. Tong Z.T., Cai M.Y., Wang X.G., Kong L.L., Mai S.J., Liu Y.H., Zhang H.B., Liao Y.J., Zheng F., Zhu W., Liu T.H., Bian X.W., Guan X.Y., Lin M.C., Zeng M.S., Zeng Y.X., Kung H.F., Xie D. EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin. Oncogene 2012, 31:583-594.
87. Cristofanilli M., Budd G.T., Ellis M.J., Stopeck A., Matera J., Miller M.C., Reuben J.M., Doyle G.V., Allard W.J., Terstappen L.W., Hayes D.F. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 2004, 351:781-791.
88. Wulfing P., Borchard J., Buerger H., Heidl S., Zanker K.S., Kiesel L., Brandt B. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin. Cancer Res. 2006, 12:1715-1720.
89. Cohen S.J., Punt C.J., Iannotti N., Saidman B.H., Sabbath K.D., Gabrail N.Y., Picus J., Morse M., Mitchell E., Miller M.C., Doyle G.V., Tissing H., Terstappen L.W., Meropol N.J. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J. Clin. Oncol. 2008, 26:3213-3221.
90. Rahbari N.N., Aigner M., Thorlund K., Mollberg N., Motschall E., Jensen K., Diener M.K., Buchler M.W., Koch M., Weitz J. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology 2010, 138:1714-1726.
91. Danila D.C., Fleisher M., Scher H.I. Circulating tumor cells as biomarkers in prostate cancer. Clin. Cancer Res. 2011, 17:3903-3912.
92. Ghossein R.A., Scher H.I., Gerald W.L., Kelly W.K., Curley T., Amsterdam A., Zhang Z.F., Rosai J. Detection of circulating tumor cells in patients with localized and metastatic prostatic carcinoma: clinical implications. J. Clin. Oncol. 1995, 13:1195-1200.
93. Scher H.I., Jia X., de Bono J.S., Fleisher M., Pienta K.J., Raghavan D., Heller G. Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol. 2009, 10:233-239.
94. Brakenhoff R.H., Stroomer J.G., ten Brink C., de Bree R., Weima S.M., Snow G.B., van Dongen G.A. Sensitive detection of squamous cells in bone marrow and blood of head and neck cancer patients by E48 reverse transcriptase-polymerase chain reaction. Clin. Cancer Res. 1999, 5:725-732.
95. Partridge M., Brakenhoff R., Phillips E., Ali K., Francis R., Hooper R., Lavery K., Brown A., Langdon J. Detection of rare disseminated tumor cells identifies head and neck cancer patients at risk of treatment failure. Clin. Cancer Res. 2003, 9:5287-5294.
96. Wollenberg B., Walz A., Kolbow K., Pauli C., Chaubal S., Andratschke M. Clinical relevance of circulating tumour cells in the bone marrow of patients with SCCHN. Onkologie 2004, 27:358-362.
97. Winter S.C., Stephenson S.A., Subramaniam S.K., Paleri V., Ha K., Marnane C., Krishnan S., Rees G. Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma. BMC Cancer 2009, 9:424.
98. Jatana K.R., Balasubramanian P., Lang J.C., Yang L., Jatana C.A., White E., Agrawal A., Ozer E., Schuller D.E., Teknos T.N., Chalmers J.J. Significance of circulating tumor cells in patients with squamous cell carcinoma of the head and neck: initial results. Arch. Otolaryngol. Head Neck Surg. 2011, 136:1274-1279.
99. Hristozova T., Konschak R., Stromberger C., Fusi A., Liu Z., Weichert W., Stenzinger A., Budach V., Keilholz U., Tinhofer I. The presence of circulating tumor cells (CTCs) correlates with lymph node metastasis in nonresectable squamous cell carcinoma of the head and neck region (SCCHN). Ann. Oncol. 2011, 22:1878-1885.
100. Aktas B., Tewes M., Fehm T., Hauch S., Kimmig R., Kasimir-Bauer S. Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 2009, 11:R46.
101. He H., Yang X., Davidson A.J., Wu D., Marshall F.F., Chung L.W., Zhau H.E., Wang R. Progressive epithelial to mesenchymal transitions in ARCaP E prostate cancer cells during xenograft tumor formation and metastasis. Prostate 2011, 70:518-528.
102. Armstrong A.J., Marengo M.S., Oltean S., Kemeny G., Bitting R.L., Turnbull J.D., Herold C.I., Marcom P.K., George D.J., Garcia-Blanco M.A. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol. Cancer Res. 2011, 9:997-1007.
103. Mostert B., Kraan J., Sieuwerts A.M., van der Spoel P., Bolt-de Vries J., Prager-van der Smissen W.J., Smid M., Timmermans A.M., Martens J.W., Gratama J.W., Foekens J.A., Sleijfer S. CD49f-based selection of circulating tumor cells (CTCs) improves detection across breast cancer subtypes. Cancer Lett. 2012, 319:49-55.
104. Raimondi C., Gradilone A., Naso G., Vincenzi B., Petracca A., Nicolazzo C., Palazzo A., Saltarelli R., Spremberg F., Cortesi E., Gazzaniga P. Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Res. Treat. 2011, 130:449-455.
105. Lecharpentier A., Vielh P., Perez-Moreno P., Planchard D., Soria J.C., Farace F. Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer. Br. J. Cancer 2011, 105:1338-1341.
106. T. Hristozova, R. Konschak, V. Budach, I. Tinhofer, A simple multicolor flow cytometry protocol for detection and molecular characterization of circulating tumor cells in epithelial cancers, Cytometry A, 81 (2012) 489-495.
107. Hirsch H.A., Iliopoulos D., Tsichlis P.N., Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009, 69:7507-7511.
108. Vazquez-Martin A., Oliveras-Ferraros C., Del Barco S., Martin-Castillo B., Menendez J.A. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res. Treat. 2011, 126:355-364.
109. Gupta P.B., Onder T.T., Jiang G., Tao K., Kuperwasser C., Weinberg R.A., Lander E.S. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009, 138:645-659.
110. Zhi Q.M., Chen X.H., Ji J., Zhang J.N., Li J.F., Cai Q., Liu B.Y., Gu Q.L., Zhu Z.G., Yu Y.Y. Salinomycin can effectively kill ALDH(high) stem-like cells on gastric cancer. Biomed. Pharmacother. 2011, 65:509-515.
111. Ketola K., Hilvo M., Hyotylainen T., Vuoristo A., Ruskeepaa A.L., Oresic M., Kallioniemi O., Iljin K. Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br. J. Cancer 2012, 106:99-106.
112. Dong T.T., Zhou H.M., Wang L.L., Feng B., Lv B., Zheng M.H. Salinomycin selectively targets 'CD133+' cell subpopulations and decreases malignant traits in colorectal cancer lines. Ann. Surg. Oncol. 2011, 18:1797-1804.
113. Beug H. Breast cancer stem cells: eradication by differentiation therapy?. Cell 2009, 138:623-625.
114. Riccioni R., Dupuis M.L., Bernabei M., Petrucci E., Pasquini L., Mariani G., Cianfriglia M., Testa U. The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol. Dis. 2010, 45:86-92.
115. Fuchs D., Daniel V., Sadeghi M., Opelz G., Naujokat C. Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells. Biochem. Biophys. Res. Commun. 2010, 394:1098-1104.
116. Basu D., Montone K.T., Wang L.P., Gimotty P.A., Hammond R., Diehl J.A., Rustgi A.K., Lee J.T., Rasanen K., Weinstein G.S., Herlyn M. Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas. Cell Cycle 2011, 10:2008-2016.
117. Boehmerle W., Endres M. Salinomycin induces calpain and cytochrome c-mediated neuronal cell death. Cell Death Dis. 2011, 2:e168.
118. Yakisich J.S. Challenges and limitations of targeting cancer stem cells and/or the tumour microenvironment. Drugs Therapy Stud. 2012, 2:48-55.
119. Li C., Feng Y., Coukos G., Zhang L. Therapeutic microRNA strategies in human cancer. AAPS J. 2009, 11:747-757.
120. X. Lin, R. Gao, Y. Zhang, N. Qi, K. Zhang, H. He, X. Tang, Lipid nanoparticles for chemotherapeutic applications: strategies to improve anticancer efficacy, Expert Opin. Drug Deliv., 9 (2012) 767-781.
121. Waite C.L., Roth C.M. Nanoscale drug delivery systems for enhanced drug penetration into solid tumors: current progress and opportunities. Crit. Rev. Biomed. Eng. 2012, 40:21-41.
122. Piao L., Zhang M., Datta J., Xie X., Su T., Li H., Teknos T.N., Pan Q. Lipid-based nanoparticle delivery of pre-miR-107 inhibits the tumorigenicity of head and neck squamous cell carcinoma. Mol. Ther. 2012, 20:1261-1269.
123. Rothschild B.L., Shim A.H., Ammer A.G., Kelley L.C., Irby K.B., Head J.A., Chen L., Varella-Garcia M., Sacks P.G., Frederick B., Raben D., Weed S.A. Cortactin overexpression regulates actin-related protein 2/3 complex activity, motility, and invasion in carcinomas with chromosome 11q13 amplification. Cancer Res. 2006, 66:8017-8025.
124. Sun Q., Prasad R., Rosenthal E., Katiyar S.K. Grape seed proanthocyanidins inhibit the invasive potential of head and neck cutaneous squamous cell carcinoma cells by targeting EGFR expression and epithelial-to-mesenchymal transition. BMC Complement Altern. Med. 2011, 11:134.
125. Xu H., Stabile L.P., Gubish C.T., Gooding W.E., Grandis J.R., Siegfried J.M. Dual blockade of EGFR and c-Met abrogates redundant signaling and proliferation in head and neck carcinoma cells. Clin. Cancer Res. 2011, 17:4425-4438.
126. Bruzzese F., Leone A., Rocco M., Carbone C., Piro G., Caraglia M., Di Gennaro E., Budillon A. HDAC inhibitor vorinostat enhances the antitumor effect of gefitinib in squamous cell carcinoma of head and neck by modulating ErbB receptor expression and reverting EMT. J. Cell. Physiol. 2011, 226:2378-2390.
127. Yoshikawa M., Hishikawa K., Marumo T., Fujita T. Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells. J. Am. Soc. Nephrol. 2007, 18:58-65.
128. Thiery J.P., Acloque H., Huang R.Y., Nieto M.A. Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139:871-890.
129. Rizzo P., Osipo C., Foreman K., Golde T., Osborne B., Miele L. Rational targeting of Notch signaling in cancer. Oncogene 2008, 27:5124-5131.
130. Gjerdrum C., Tiron C., Hoiby T., Stefansson I., Haugen H., Sandal T., Collett K., Li S., McCormack E., Gjertsen B.T., Micklem D.R., Akslen L.A., Glackin C., Lorens J.B. Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc. Natl. Acad. Sci. USA 2010, 107:1124-1129.
131. Egeblad M., Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2002, 2:161-174.
132. Hong S.D., Hong S.P., Lee J.I., Lim C.Y. Expression of matrix metalloproteinase-2 and -9 in oral squamous cell carcinomas with regard to the metastatic potential. Oral Oncol. 2000, 36:207-213.
133. O-Charoenrat P., Rhys-Evans P.H., Eccles S.A. Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck. Arch. Otolaryngol. Head Neck Surg. 2001, 127:813-820.
134. O-Charoenrat P., Wongkajornsilp A., Rhys-Evans P.H., Eccles S.A. Signaling pathways required for matrix metalloproteinase-9 induction by betacellulin in head-and-neck squamous carcinoma cells. Int. J. Cancer 2004, 111:174-183.
135. Sinpitaksakul S.N., Pimkhaokham A., Sanchavanakit N., Pavasant P. TGF-beta1 induced MMP-9 expression in HNSCC cell lines via Smad/MLCK pathway. Biochem. Biophys. Res. Commun. 2008, 371:713-718.
136. Sterz C.M., Kulle C., Dakic B., Makarova G., Bottcher M.C., Bette M., Werner J.A., Mandic R. A basal-cell-like compartment in head and neck squamous cell carcinomas represents the invasive front of the tumor and is expressing MMP-9. Oral Oncol. 2010, 46:116-122.
137. Fingleton B. MMPs as therapeutic targets - still a viable option?. Semin. Cell Dev. Biol. 2008, 19:61-68.
138. Chaudhary A.K., Singh M., Bharti A.C., Asotra K., Sundaram S., Mehrotra R. Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck. J. Biomed. Sci. 2010, 17:10.
139. Gialeli C., Theocharis A.D., Karamanos N.K. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J. 2011, 278:16-27.
140. Haddad Y., Choi W., McConkey D.J. Delta-crystallin enhancer binding factor 1 controls the epithelial to mesenchymal transition phenotype and resistance to the epidermal growth factor receptor inhibitor erlotinib in human head and neck squamous cell carcinoma lines. Clin. Cancer Res. 2009, 15:532-542.
141. Yang M.H., Chang S.Y., Chiou S.H., Liu C.J., Chi C.W., Chen P.M., Teng S.C., Wu K.J. Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer. Oncogene 2007, 26:1459-1467.
142. Ramos D.M., Dang D., Sadler S. The role of the integrin alpha v beta6 in regulating the epithelial to mesenchymal transition in oral cancer. Anticancer Res. 2009, 29:125-130.
143. Wilkins-Port C.E., Higgins P.J. Regulation of extracellular matrix remodeling following transforming growth factor-beta1/epidermal growth factor-stimulated epithelial-mesenchymal transition in human premalignant keratinocytes. Cells Tissues Organs 2007, 185:116-122.
144. Nguyen P.T., Kudo Y., Yoshida M., Kamata N., Ogawa I., Takata T. N-cadherin expression is involved in malignant behavior of head and neck cancer in relation to epithelial-mesenchymal transition. Histol. Histopathol. 2011, 26:147-156.
145. M. Dennis, G. Wang, J. Luo, Y. Lin, M. Dohadwala, E. Abemayor, D.A. Elashoff, S. Sharma, S.M. Dubinett, M.A. John, St., Snail controls the mesenchymal phenotype and drives erlotinib resistance in oral epithelial and head and neck squamous cell carcinoma cells, Otolaryngol. Head Neck Surg., 2012.
146. Grille S.J., Bellacosa A., Upson J., Klein-Szanto A.J., van Roy F., Lee-Kwon W., Donowitz M., Tsichlis P.N., Larue L. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 2003, 63:2172-2178.
147. Bleijerveld O.B., Brakenhoff R.H., Schaaij-Visser T.B., Damen J.M., Altelaar A.F., Heck A.J., Leemans C.R., Slijper M. Protein signatures associated with tumor cell dissemination in head and neck cancer. J. Proteomics 2011, 74:558-566.
148. Frederick B.A., Helfrich B.A., Coldren C.D., Zheng D., Chan D., Bunn P.A., Raben D. Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Mol. Cancer Ther. 2007, 6:1683-1691.
149. Yang J., Mani S.A., Donaher J.L., Ramaswamy S., Itzykson R.A., Come C., Savagner P., Gitelman I., Richardson A., Weinberg R.A. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004, 117:927-939.
150. St John M.A., Dohadwala M., Luo J., Wang G., Lee G., Shih H., Heinrich E., Krysan K., Walser T., Hazra S., Zhu L., Lai C., Abemayor E., Fishbein M., Elashoff D.A., Sharma S., Dubinett S.M. Proinflammatory mediators upregulate snail in head and neck squamous cell carcinoma. Clin. Cancer Res. 2009, 15:6018-6027.
151. Katafiasz D., Smith L.M., Wahl J.K. Slug (SNAI2) expression in oral SCC cells results in altered cell-cell adhesion and increased motility. Cell Adh. Migr. 2011, 5:315-322.
152. Dohadwala M., Wang G., Heinrich E., Luo J., Lau O., Shih H., Munaim Q., Lee G., Hong L., Lai C., Abemayor E., Fishbein M.C., Elashoff D.A., Dubinett S.M., St John M.A. The role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. Otolaryngol. Head Neck Surg. 2010, 142:753-759.
153. Liang X., Zheng M., Jiang J., Zhu G., Yang J., Tang Y. Hypoxia-inducible factor-1 alpha, in association with TWIST2 and SNIP1, is a critical prognostic factor in patients with tongue squamous cell carcinoma. Oral Oncol. 2011, 47:92-97.
154. Danielsson K., Wahlin Y.B., Coates P.J., Nylander K. Increased expression of Smad proteins, and in particular Smad3, in oral lichen planus compared to normal oral mucosa. J. Oral Pathol. Med. 2010, 39:639-644.
155. C. Cao, Y. Chen, R. Massod, U.K. Sinha, A. Kobielak, Alpha-catulin marks the invasion front of squamous cell carcinoma and is important for tumor cell metastasis, Mol. Cancer Res., 2012.
156. Onoue T., Uchida D., Begum N.M., Tomizuka Y., Yoshida H., Sato M. Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells. Int. J. Oncol. 2006, 29:1133-1138.
157. Taki M., Higashikawa K., Yoneda S., Ono S., Shigeishi H., Nagayama M., Kamata N. Up-regulation of stromal cell-derived factor-1alpha and its receptor CXCR4 expression accompanied with epithelial-mesenchymal transition in human oral squamous cell carcinoma. Oncol. Rep. 2008, 19:993-998.
158. C. Canino, F. Mori, A. Cambria, A. Diamantini, S. Germoni, G. Alessandrini, G. Borsellino, R. Galati, L. Battistini, R. Blandino, F. Facciolo, G. Citro, S. Strano, P. Muti, G. Blandino, M. Cioce, SASP mediates chemoresistance and tumor-initiating-activity of mesothelioma cells, Oncogene 31 (2012) 3148-3163.
159. Liu S., Dontu G., Mantle I.D., Patel S., Ahn N.S., Jackson K.W., Suri P., Wicha M.S. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006, 66:6063-6071.
160. Prince M.E., Sivanandan R., Kaczorowski A., Wolf G.T., Kaplan M.J., Dalerba P., Weissman I.L., Clarke M.F., Ailles L.E. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc. Natl. Acad. Sci. USA 2007, 104:973-978.
161. Molofsky A.V., Pardal R., Iwashita T., Park I.K., Clarke M.F., Morrison S.J. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 2003, 425:962-967.
162. Jiang L., Li J., Song L. Bmi-1, stem cells and cancer. Acta Biochim. Biophys. Sin. (Shanghai) 2009, 41:527-534.
163. Guo B.H., Feng Y., Zhang R., Xu L.H., Li M.Z., Kung H.F., Song L.B., Zeng M.S. Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer. Mol. Cancer 2011, 10:10.
164. Vormittag L., Thurnher D., Geleff S., Pammer J., Heiduschka G., Brunner M., Grasl M., Erovic B.M. Co-expression of Bmi-1 and podoplanin predicts overall survival in patients with squamous cell carcinoma of the head and neck treated with radio(chemo)therapy. Int. J. Radiat. Oncol. Biol. Phys. 2009, 73:913-918.
165. Harper L.J., Piper K., Common J., Fortune F., Mackenzie I.C. Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma. J. Oral Pathol. Med. 2007, 36:594-603.
166. Leung E.L., Fiscus R.R., Tung J.W., Tin V.P., Cheng L.C., Sihoe A.D., Fink L.M., Ma Y., Wong M.P. Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One 2010, 5:e14062.
167. Bourguignon L.Y. CD44-mediated oncogenic signaling and cytoskeleton activation during mammary tumor progression. J. Mammary Gland Biol. Neoplasia 2001, 6:287-297.
168. Kim Y., Lee Y.S., Choe J., Lee H., Kim Y.M., Jeoung D. CD44-epidermal growth factor receptor interaction mediates hyaluronic acid-promoted cell motility by activating protein kinase C signaling involving Akt, Rac1, Phox, reactive oxygen species, focal adhesion kinase, and MMP-2. J. Biol. Chem. 2008, 283:22513-22528.
169. Monroe M.M., Anderson E.C., Clayburgh D.R., Wong M.H. Cancer stem cells in head and neck squamous cell carcinoma. J. Oncol. 2011, 2011:762780.
170. Suva M.L., Riggi N., Janiszewska M., Radovanovic I., Provero P., Stehle J.C., Baumer K., Le Bitoux M.A., Marino D., Cironi L., Marquez V.E., Clement V., Stamenkovic I. EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res. 2009, 69:9211-9218.
171. Rizzo S., Hersey J.M., Mellor P., Dai W., Santos-Silva A., Liber D., Luk L., Titley I., Carden C.P., Box G., Hudson D.L., Kaye S.B., Brown R. Ovarian cancer stem cell-like side populations are enriched following chemotherapy and overexpress EZH2. Mol. Cancer Ther. 2011, 10:325-335.
172. Li C., Wu J.J., Hynes M., Dosch J., Sarkar B., Welling T.H., Pasca di Magliano M., Simeone D.M. C-Met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology 2011, 141:2218-2227.
173. Sun S., Wang Z. Head neck squamous cell carcinoma c-Met(+) cells display cancer stem cell properties and are responsible for cisplatin-resistance and metastasis. Int. J. Cancer 2011, 129:2337-2348.
174. Sun B., Liu R., Xiao Z.D., Zhu X. C-MET protects breast cancer cells from apoptosis induced by sodium butyrate. PLoS One 2012, 7:e30143.
175. Mazzone M., Comoglio P.M. The Met pathway: master switch and drug target in cancer progression. FASEB J. 2006, 20:1611-1621.
176. Toiyama Y., Yasuda H., Saigusa S., Matushita K., Fujikawa H., Tanaka K., Mohri Y., Inoue Y., Goel A., Kusunoki M. Co-expression of hepatocyte growth factor and c-Met predicts peritoneal dissemination established by autocrine hepatocyte growth factor/c-Met signaling in gastric cancer. Int. J. Cancer 2012, 130:2912-2921.
177. H.M. Meng, P. Zheng, X.Y. Wang, C. Liu, H.M. Sui, S.J. Wu, J. Zhou, Y.Q. Ding, J.M. Li, Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancer, Cancer Biol. Ther. 9 (2010).
178. Chiou S.H., Wang M.L., Chou Y.T., Chen C.J., Hong C.F., Hsieh W.J., Chang H.T., Chen Y.S., Lin T.W., Hsu H.S., Wu C.W. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 2010, 70:10433-10444.
179. Chiou S.H., Yu C.C., Huang C.Y., Lin S.C., Liu C.J., Tsai T.H., Chou S.H., Chien C.S., Ku H.H., Lo J.F. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin. Cancer Res. 2008, 14:4085-4095.
180. M. Zbinden, A. Duquet, A. Lorente-Trigos, S.N. Ngwabyt, I. Borges, A. Ruiz i Altaba, NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53, EMBO J 29 (2010) 2659-2674.
181. Leong K.G., Niessen K., Kulic I., Raouf A., Eaves C., Pollet I., Karsan A. Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J. Exp. Med. 2007, 204:2935-2948.
182. Timmerman L.A., Grego-Bessa J., Raya A., Bertran E., Perez-Pomares J.M., Diez J., Aranda S., Palomo S., McCormick F., Izpisua-Belmonte J.C., de la Pompa J.L. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Gene Dev. 2004, 18:99-115.
183. Wang Z., Li Y., Kong D., Banerjee S., Ahmad A., Azmi A.S., Ali S., Abbruzzese J.L., Gallick G.E., Sarkar F.H. Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res. 2009, 69:2400-2407.
184. Atsumi N., Ishii G., Kojima M., Sanada M., Fujii S., Ochiai A. Podoplanin, a novel marker of tumor-initiating cells in human squamous cell carcinoma A431. Biochem. Biophys. Res. Commun. 2008, 373:36-41.
185. Yilmaz M., Christofori G. Mechanisms of motility in metastasizing cells. Mol. Cancer Res. 2010, 8:629-642.
186. Stein U., Arlt F., Walther W., Smith J., Waldman T., Harris E.D., Mertins S.D., Heizmann C.W., Allard D., Birchmeier W., Schlag P.M., Shoemaker R.H. The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer. Gastroenterology 2006, 131:1486-1500.
187. Harris M.A., Yang H., Low B.E., Mukherjee J., Guha A., Bronson R.T., Shultz L.D., Israel M.A., Yun K. Cancer stem cells are enriched in the side population cells in a mouse model of glioma. Cancer Res. 2008, 68:10051-10059.
188. Hwang W.L., Yang M.H., Tsai M.L., Lan H.Y., Su S.H., Chang S.C., Teng H.W., Yang S.H., Lan Y.T., Chiou S.H., Wang H.W. SNAIL regulates interleukin-8 expression, stem cell-like activity, and tumorigenicity of human colorectal carcinoma cells. Gastroenterology 2011, 141:279-291.
189. Lin C.Y., Tsai P.H., Kandaswami C.C., Lee P.P., Huang C.J., Hwang J.J., Lee M.T. Matrix metalloproteinase-9 cooperates with transcription factor Snail to induce epithelial-mesenchymal transition. Cancer Sci. 2011, 102:815-827.
190. Dang H., Ding W., Emerson D., Rountree C.B. Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics. BMC Cancer 2011, 11:396.
191. Li J., Zhou B.P. Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer 2011, 11:49.
192. Peinado H., Cano A. A hypoxic twist in metastasis. Nat Cell Biol 2008, 10:253-254.
193. Vesuna F., Lisok A., Kimble B., Raman V. Twist modulates breast cancer stem cells by transcriptional regulation of CD24 expression. Neoplasia 2009, 11:1318-1328.
194. Vesuna F., van Diest P., Chen J.H., Raman V. Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer. Biochem Biophys Res Commun 2008, 367:235-241.