A self-enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells

International Journal of Cancer

Volumn 137, Issue 11, 2015, Pages 2566-2577

  Preca, Bogdan Tiberius ^a,b   Bajdak, Karolina ^a,b   Mock, Kerstin ^a,b   Sundararajan, Vignesh ^a,b   Pfannstiel, Jessica ^a   Maurer, Jochen ^a,c   Wellner, Ulrich ^d   Hopt, Ulrich T ^a   Brummer, Tilman ^a,b   Brabletz, Simone ^a,e   Brabletz, Thomas ^e   Stemmler, Marc P ^a,e  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF FREIBURG   (Germany)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^e UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

cancer stem cells; differential splicing; drug resistance; epithelial mesenchymal transition (EMT); metastasis

Indexed keywords

HERMES ANTIGEN; TRANSCRIPTION FACTOR ZEB1; CD44 PROTEIN, HUMAN; ESRP1 PROTEIN, HUMAN; HOMEODOMAIN PROTEIN; RNA BINDING PROTEIN; TRANSCRIPTION FACTOR; ZEB1 PROTEIN, HUMAN;

ARTICLE; BREAST CANCER; CANCER CELL; CANCER STEM CELL; CELL MOTILITY; CELL SURVIVAL; CONTROLLED STUDY; DOWN REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; FEEDBACK SYSTEM; HUMAN; HUMAN CELL; HUMAN TISSUE; PANCREAS CANCER; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUMOR SPHEROID; BREAST TUMOR; CELL LINE; CELL TRANSFORMATION; DRUG RESISTANCE; FEMALE; GENE EXPRESSION REGULATION; GENETICS; HEK293 CELL LINE; MCF 7 CELL LINE; PANCREAS TUMOR; PATHOLOGY; TUMOR CELL LINE; TUMOR RECURRENCE;

ANTIGENS, CD44; BREAST NEOPLASMS; CELL LINE; CELL LINE, TUMOR; CELL TRANSFORMATION, NEOPLASTIC; DOWN-REGULATION; DRUG RESISTANCE, NEOPLASM; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HEK293 CELLS; HOMEODOMAIN PROTEINS; HUMANS; MCF-7 CELLS; NEOPLASM RECURRENCE, LOCAL; PANCREATIC NEOPLASMS; RNA-BINDING PROTEINS; TRANSCRIPTION FACTORS;

EID: 84941737633     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.29642     Document Type: Article

References (53)

1. Brabletz T., EMT and MET in metastasis: where are the cancer stem cells? Cancer Cell 2012; 22: 699-701.
2. Thiery JP, Sleeman JP., Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7: 131-42.
3. Yang J, Weinberg RA., Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 2008; 14: 818-29.
4. De Craene B, Berx G., Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 2013; 13: 97-110.
5. Thiery JP, Acloque H, Huang RY, et al., Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139: 871-90.
6. Spaderna S, Schmalhofer O, Wahlbuhl M, et al., The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res 2008; 68: 537-44.
7. Mani SA, Guo W, Liao MJ, et al., The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133: 704-15.
8. Morel AP, Lievre M, Thomas C, et al., Hinkal G, Ansieau S, Puisieux A., Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008; 3: e2888.
9. Wellner U, Schubert J, Burk UC, et al., The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 2009; 11: 1487-95.
10. Clarke MF, Fuller M., Stem cells and cancer: two faces of eve. Cell 2006; 124: 1111 -1 5.
11. Gupta PB, Chaffer CL, Weinberg RA., Cancer stem cells: mirage or reality? Nat Med 2009; 15: 1010 -1 2.
12. Medema JP., Cancer stem cells: the challenges ahead. Nat Cell Biol 2013; 15: 338-44.
13. Beck B, Blanpain C., Unravelling cancer stem cell potential. Nat Rev Cancer 2013; 13: 727-38.
14. Hanahan D, Weinberg RA., Hallmarks of cancer: the next generation. Cell 2011; 144: 646-74.
15. Meltzer A., Dormancy and breast cancer. J Surg Oncol 1990; 43: 181-8.
16. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al., Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100: 3983-8.
17. Collins AT, Berry PA, Hyde C, et al., Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005; 65: 10946-51.
18. Patrawala L, Calhoun T, Schneider-Broussard R, et al., Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 2006; 25: 1696-708.
19. Li C, Heidt DG, Dalerba P, et al., Identification of pancreatic cancer stem cells. Cancer Res 2007; 67: 1030-7.
20. Dalerba P, Dylla SJ, Park IK, et al., Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 2007; 104: 10158-63.
21. Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P., Ponta H. CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev 2002; 16: 3074-86.
22. Zoller M., CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer 2011; 11: 254-67.
23. Williams K, Motiani K, Giridhar PV, et al., CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches. Exp Biol Med 2013; 238: 324-38.
24. Ponta H, Sherman L, Herrlich PA., CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003; 4: 33-45.
25. Warzecha CC, Sato TK, Nabet B, et al., ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing. Mol Cell 2009; 33: 591-601.
26. Herr R, Wohrle FU, Danke C, et al., A novel MCF-10A line allowing conditional oncogene expression in 3D culture. Cell Commun Signal 2011; 9: 17.
27. Spaderna S, Schmalhofer O, Hlubek F, et al., A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology 2006; 131: 830-40.
28. Vannier C, Mock K, Brabletz T, et al., Zeb1 regulates E-cadherin and Epcam (epithelial cell adhesion molecule) expression to control cell behavior in early zebrafish development. J Biol Chem 2013; 288: 18643-59.
29. Brabletz T, Spaderna S, Kolb J, et al., Down-regulation of the homeodomain factor Cdx2 in colorectal cancer by collagen type I: an active role for the tumor environment in malignant tumor progression. Cancer Res 2004; 64: 6973-7.
30. Lee JK, Havaleshko DM, Cho H, et al., A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery. Proc Natl Acad Sci USA 2007; 104: 13086-91.
31. Park SM, Gaur AB, Lengyel E, et al., The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 2008; 22: 894-907.
32. Barretina J, Caponigro G, Stransky N, et al., The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012; 483: 603-7.
33. Sato M, Larsen JE, Lee W, et al., Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations. Mol Cancer Res 2013; 11: 638-50.
34. Clarke C, Madden SF, Doolan P, et al., Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis. Carcinogenesis 2013; 34: 2300-8.
35. Zhang G, He P, Tan H, et al., Integration of metabolomics and transcriptomics revealed a fatty acid network exerting growth inhibitory effects in human pancreatic cancer. Clin Cancer Res 2013; 19: 4983-93.
36. Zhang G, Schetter A, He P, et al., DPEP1 inhibits tumor cell invasiveness, enhances chemosensitivity and predicts clinical outcome in pancreatic ductal adenocarcinoma. PLoS One 2012; 7: e31507.
37. Brown RL, Reinke LM, Damerow MS, et al., Perez D, Chodosh LA, Yang J, Cheng C., CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression. J Clin Invest 2011; 121: 1064-74.
38. Horiguchi K, Sakamoto K, Koinuma D, et al., TGF-beta drives epithelial-mesenchymal transition through deltaEF1-mediated downregulation of ESRP. Oncogene 2012; 31: 3190-201.
39. Reinke LM, Xu Y, Cheng C., Snail represses the splicing regulator epithelial splicing regulatory protein 1 to promote epithelial-mesenchymal transition. J Biol Chem 2012; 287: 36435-42.
40. Shah AN, Summy JM, Zhang J, et al., Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol 2007; 14: 3629-37.
41. Siemens H, Jackstadt R, Hunten S, et al., miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle 2011; 10: 4256-71.
42. Mima K, Okabe H, Ishimoto T, et al., CD44s regulates the TGF-beta-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res 2012; 72: 3414-23.
43. Shi J, Zhou Z, Di W, et al., Correlation of CD44v6 expression with ovarian cancer progression and recurrence. BMC Cancer 2013; 13: 182.
44. Diaz LK, Zhou X, Wright ET, et al., CD44 expression is associated with increased survival in node-negative invasive breast carcinoma. Clin Cancer Res 2005; 11: 3309-14.
45. Pacifico MD, Grover R, Richman PI, et al., CD44v3 levels in primary cutaneous melanoma are predictive of prognosis: assessment by the use of tissue microarray. Int J Cancer 2006; 118: 1460-4.
46. Tolboom TC, Huidekoper AL, Kramer IM, et al., Correlation between expression of CD44 splice variant v8-v9 and invasiveness of fibroblast-like synoviocytes in an in vitro system. Clin Exp Rheumatol 2004; 22: 158-64.
47. Sato S, Miyauchi M, Kato M, et al., Upregulated CD44v9 expression inhibits the invasion of oral squamous cell carcinoma cells. Pathobiology 2004; 71: 171-5.
48. Suzuki H, Yamashiro K., Reduced expression of CD44 v3 and v6 is related to invasion in lung adenocarcinoma. Lung Cancer 2002; 38: 137-41.
49. Todaro M, Gaggianesi M, Catalano V, et al., CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell 2014; 14: 342-56.
50. Zeilstra J, Joosten SP, van Andel H, et al., Stem cell CD44v isoforms promote intestinal cancer formation in Apc(min) mice downstream of Wnt signaling. Oncogene 2014; 33: 665-70.
51. Xu Y, Gao XD, Lee JH, et al., Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing. Genes Dev 2014; 28: 1191-203.
52. Burk U, Schubert J, Wellner U, et al., 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: 582-9.
53. Susuki D, Kimura S, Naganuma S, et al., Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma. Cancer Sci 2011; 102: 2164-71.