The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs

Nature Cell Biology

Volumn 11, Issue 12, 2009, Pages 1487-1495

  Wellner, Ulrich ^a   Schubert, Jörg ^a   Burk, Ulrike C ^a   Schmalhofer, Otto ^a   Zhu, Feng ^a   Sonntag, Annika ^a   Waldvogel, Bettina ^a   Vannier, Corinne ^a   Darling, Douglas ^b   Hausen, Axel Zur ^a   Brunton, Valerie G ^c   Morton, Jennifer ^d   Sansom, Owen ^d   Schüler, Julia ^e   Stemmler, Marc P ^f   Herzberger, Christoph ^a   Hopt, Ulrich ^a   Keck, Tobias ^a   Brabletz, Simone ^a   Brabletz, Thomas ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF LOUISVILLE   (United States)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

^d BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

^e CHARLES RIVER LABORATORIES   (United States)

^f MAX PLANCK INSTITUTE OF IMMUNOBIOLOGY AND EPIGENETICS   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

HOMEODOMAIN PROTEIN; KRUPPEL LIKE FACTOR; MICRORNA; TRANSCRIPTION FACTOR; ZEB1 PROTEIN, HUMAN; ZEB1 PROTEIN, MOUSE;

ANIMAL; ARTICLE; CELL DIFFERENTIATION; CYTOLOGY; DRUG SCREENING; EPITHELIUM CELL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; HUMAN; MALE; MESENCHYMAL STEM CELL; METABOLISM; MOUSE; NEOPLASM; NUCLEOTIDE SEQUENCE; NUDE MOUSE; PATHOLOGY; SEQUENCE ALIGNMENT; TUMOR CELL LINE;

ANIMALS; BASE SEQUENCE; CELL DIFFERENTIATION; CELL LINE, TUMOR; EPITHELIAL CELLS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HOMEODOMAIN PROTEINS; HUMANS; KRUPPEL-LIKE TRANSCRIPTION FACTORS; MALE; MESENCHYMAL STEM CELLS; MICE; MICE, NUDE; MICRORNAS; NEOPLASMS; SEQUENCE ALIGNMENT; TRANSCRIPTION FACTORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 73049110243     PISSN: 14657392     EISSN: 14764679     Source Type: Journal    
DOI: 10.1038/ncb1998     Document Type: Article

References (45)

1. Barrallo-Gimeno, A. & Nieto, M. A. The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132, 3151-3161 (2005). (Pubitemid 41167144)
2. Berx, G., Raspe, E., Christofori, G., Thiery, J. P. & Sleeman, J. P. Pre-EMTing metastasis? Recapitulation of morphogenetic processes in cancer. Clin. Exp. Metastasis 24, 587-597 (2007). (Pubitemid 50000849)
3. Peinado, H., Olmeda, D. & Cano, A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nature Rev. Cancer 7, 415-428 (2007). (Pubitemid 46809165)
4. Spaderna, S. et al. The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res. 68, 537-544 (2008). (Pubitemid 351380082)
5. Dalerba, P., Cho, R. W. & Clarke, M. F. Cancer stem cells: models and concepts. Annu. Rev. Med. 58, 267-284 (2007). (Pubitemid 46706514)
6. Brabletz, T., Jung, A., Spaderna, S., Hlubek, F. & Kirchner, T. Opinion: migrating cancer stem cells-an integrated concept of malignant tumour progression. Nature Rev. Cancer 5, 744-749 (2005). (Pubitemid 41486367)
7. Brabletz, T. et al. Variable beta-catenin expression in colorectal cancer indicates a tumor progression driven by the tumor environment. Proc. Natl Acad. Sci. USA 98, 10356-10361 (2001). (Pubitemid 32803024)
8. Mani, S. A. et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133, 704-715 (2008). (Pubitemid 351636299)
9. Esquela-Kerscher, A. & Slack, F. J. Oncomirs-microRNAs with a role in cancer. Nature Rev. Cancer 6, 259-269 (2006).
10. Burk, U. et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 9, 582-589 (2008). (Pubitemid 351772923)
11. Christoffersen, N. R., Silahtaroglu, A., Orom, U. A., Kauppinen, S. & Lund, A. H. miR-200b mediates post-transcriptional repression of ZFHX1B. RNA 13, 1172-1178 (2007). (Pubitemid 47080461)
12. Gregory, P. A. et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biol. 10, 593-601 (2008). (Pubitemid 351627379)
13. Hurteau, G. J., Carlson, J. A., Spivack, S. D. & Brock, G. J. Overexpression of the microRNA hsa?miR?200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin. Cancer Res. 67, 7972-7976 (2007). (Pubitemid 47395127)
14. Korpal, M., Lee, E. S., Hu, G. & Kang, Y. The miR-200 family inhibits epithelialmesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J. Biol. Chem. 283, 14910-14914 (2008).
15. Park, S. M., Gaur, A. B., Lengyel, E. & Peter, M. E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22, 894-907 (2008). (Pubitemid 351482843)
16. Bracken, C. P. et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 68, 7846-7854 (2008).
17. Yi, R., Poy, M. N., Stoffel, M. & Fuchs, E. A skin microRNA promotes differentiation by repressing 'stemness'. Nature 452, 225-229 (2008). (Pubitemid 351380241)
18. Spaderna, S. et al. A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology 131, 830-840 (2006). (Pubitemid 44307069)
19. Winter, J. M. et al. Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin. Cancer Res. 14, 412-418 (2008). (Pubitemid 351226108)
20. Martínez-Romero, C. et al. The epigenetic regulators Bmi1 and Ring1B are differentially regulated in pancreatitis and pancreatic ductal adenocarcinoma. J. Path. 219, 205-213 (2009).
21. Gou, S. et al. Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas 34, 429-435 (2007). (Pubitemid 46725784)
22. Li, C. et al. Identification of pancreatic cancer stem cells. Cancer Res. 67, 1030-1037 (2007).
23. Li, Q. Q. et al. Twist1-mediated adriamycin-induced epithelial- mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin. Cancer Res. 15, 2657-2665 (2009).
24. Vega, S. et al. Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 18, 1131-1143 (2004). (Pubitemid 38669034)
25. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872 (2007). (Pubitemid 350138099)
26. Park, I.-k. et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423, 302-305 (2003).
27. Godlewski, J. et al. Targeting of the Bmi-1 oncogene/stem cell renewal factor by micro-RNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 68, 9125-9130 (2008).
28. Bar, M. et al. MicroRNA discovery and profiling in human embryonic stem cells by deep sequencing of small RNA libraries. Stem Cells 26, 2496-2505 (2008).
29. Shah, A. N. et al. Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann. Surg. Oncol. 14, 3629-3637 (2007). (Pubitemid 350160137)
30. Hingorani, S. R. et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7, 469-483 (2005). (Pubitemid 40719130)
31. Morel, A. P. et al. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE 3, e2888 (2008).
32. Peter, M. E. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle 8, 843-852 (2009).
33. Shimono, Y. et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138, 592-603 (2009).
34. Ben-Porath, I. et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nature Genet. 40, 499-507 (2008). (Pubitemid 351601215)
35. Brabletz, T. 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. 64, 6973-6977 (2004). (Pubitemid 39331007)
36. Brummelkamp, T. R., Bernards, R. & Agami, R. A system for stable expression of short interfering RNAs in mammalian cells. Science 296, 550-553 (2002). (Pubitemid 34408678)
37. Hlubek, F., Jung, A., Kotzor, N., Kirchner, T. & Brabletz, T. Expression of the invasion factor laminin γ2 in colorectal carcinomas is regulated by β-catenin. Cancer Res. 61, 8089-8093 (2001). (Pubitemid 33091595)
38. Hotz, B. et al. Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer. Clin. Cancer Res. 13, 4769-4776 (2007). (Pubitemid 47294783)
39. Shoemaker, R. H. The NCI60 human tumour cell line anticancer drug screen. Nature Rev. Cancer 6, 813-823 (2006). (Pubitemid 44450469)
40. Saeed, A. I. et al. TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34, 374-378 (2003). (Pubitemid 36184095)
41. Tusher, V. G., Tibshirani, R. & Chu, G. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl Acad. Sci. USA 98, 5116-5121 (2001). (Pubitemid 32397092)
42. Krutzfeldt, J. et al. Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res. 35, 2885-2892 (2007). (Pubitemid 47073627)
43. Schreiber, T. S. et al. Successful growth of mouse pancreatic ductal cells: functional properties of the ki-RAS (G12V) oncogene. Gastroenterology 127, 250-260 (2004).
44. Smith, V., Wirth, G. J., Fiebig, H. H. & Burger, A. M. Tissue microarrays of human tumor xenografts: characterization of proteins involved in migration and angiogenesis for applications in the development of targeted anticancer agents. Cancer Genomics Proteomics 5, 263-273 (2008).
45. Darling, D. S. et al. Expression of Zfhep/delta Ef1 protein in palate, neural progenitors, and differentiated neurons. Gene Expr. Patterns 3, 709-717 (2003). (Pubitemid 37451852)