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

Nature Cell Biology
Ulrich WellnerThomas Brabletz

Abstract

Invasion and metastasis of carcinomas is promoted by the activation of the embryonic 'epithelial to mesenchymal transition' (EMT) program, which triggers cellular mobility and subsequent dissemination of tumour cells. We recently showed that the EMT-activator ZEB1 (zinc finger E-box binding homeobox 1) is a crucial promoter of metastasis and demonstrated that ZEB1 inhibits expression of the microRNA-200 (miR-200) family, whose members are strong inducers of epithelial differentiation. Here, we report that ZEB1 not only promotes tumour cell dissemination, but is also necessary for the tumour-initiating capacity of pancreatic and colorectal cancer cells. We show that ZEB1 represses expression of stemness-inhibiting miR-203 and that candidate targets of miR-200 family members are also stem cell factors, such as Sox2 and Klf4. Moreover, miR-200c, miR-203 and miR-183 cooperate to suppress expression of stem cell factors in cancer cells and mouse embryonic stem (ES) cells, as demonstrated for the polycomb repressor Bmi1. We propose that ZEB1 links EMT-activation and stemness-maintenance by suppressing stemness-inhibiting microRNAs (miRNAs) and thereby is a promoter of mobile, migrating cancer stem cells. Thus, targeting the ZEB1-miR-...Continue Reading

References

Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·V G TusherG Chu
Aug 30, 2001·Proceedings of the National Academy of Sciences of the United States of America·T BrabletzT Kirchner
Mar 23, 2002·Science·Thijn R BrummelkampReuven Agami
Mar 5, 2003·BioTechniques·A I SaeedJ Quackenbush
Dec 4, 2003·Gene Expression Patterns : GEP·Douglas S DarlingJoseph P Feller
May 25, 2004·Genes & Development·Sonia VegaM Angela Nieto
Jun 29, 2005·Development·Alejandro Barrallo-Gimeno, M Angela Nieto
Sep 9, 2005·Nature Reviews. Cancer·Thomas BrabletzThomas Kirchner
Mar 25, 2006·Nature Reviews. Cancer·Aurora Esquela-Kerscher, Frank J Slack
Sep 23, 2006·Nature Reviews. Cancer·Robert H Shoemaker
Sep 28, 2006·Annual Review of Medicine·Piero DalerbaMichael F Clarke
Feb 7, 2007·Cancer Research·Chenwei LiDiane M Simeone
Apr 19, 2007·Nucleic Acids Research·Jan KrützfeldtMarkus Stoffel
May 18, 2007·Nature Reviews. Cancer·Héctor PeinadoAmparo Cano
Jun 23, 2007·RNA·Nanna Rønbjerg ChristoffersenAnders H Lund
Aug 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Birgit HotzHubert G Hotz
Oct 3, 2007·Annals of Surgical Oncology·Ami N ShahGary E Gallick
Nov 6, 2007·Clinical & Experimental Metastasis·Geert BerxJonathan P Sleeman
Jan 18, 2008·Cancer Research·Simone SpadernaThomas Brabletz
Jan 29, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jordan M WinterChristine A Iacobuzio-Donahue
Aug 7, 2008·PloS One·Anne-Pierre MorelAlain Puisieux
Apr 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qing-Quan LiZu-De Xu
Jul 9, 2009·The Journal of Pathology·Carles Martínez-RomeroInmaculada Hernández-Muñoz

❮ Previous
Next ❯

Citations

Aug 29, 2012·Cellular and Molecular Life Sciences : CMLS·Huiping Liu
May 30, 2013·Cellular and Molecular Life Sciences : CMLS·Luis A AparicioAngélica Figueroa
Jan 15, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Achim Aigner
Dec 25, 2010·Basic Research in Cardiology·Kisho Ohtani, Stefanie Dimmeler
Oct 13, 2010·Cancer Metastasis Reviews·Ming ShiNing Guo
Feb 4, 2012·Cancer Metastasis Reviews·Adrian Biddle, Ian C Mackenzie
Jun 16, 2012·Cancer Metastasis Reviews·Jonathan P Sleeman
Apr 1, 2010·Journal of Mammary Gland Biology and Neoplasia·Chad J CreightonJeffrey M Rosen
May 26, 2010·Journal of Mammary Gland Biology and Neoplasia·Josephine A WrightGregory J Goodall
Mar 31, 2011·Journal of Mammary Gland Biology and Neoplasia·Jenny G ParvaniWilliam P Schiemann
Feb 2, 2012·Journal of Mammary Gland Biology and Neoplasia·Scott Valastyan
Feb 22, 2012·Journal of Mammary Gland Biology and Neoplasia·Erin N HoweJennifer K Richer
Apr 25, 2012·Frontiers of Medicine·Ji Qi, David Mu
Feb 4, 2012·Molecular Biotechnology·Rosalinda Madonna
Aug 29, 2012·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Chao Ni, Jian Huang
Sep 17, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Eileen L HeinrichSteven M Dubinett
Mar 26, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jun Dou, Ning Gu
Mar 9, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ioannis A Voutsadakis
Mar 27, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Wei-Xian ChenJian-Hua Zhao
May 21, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hassan FazilatyBabak Behnam
Sep 27, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Miguel A VarelaMatthew J A Wood
Dec 4, 2012·Cancer Letters·Delphine Tamara Marie-EgyptienneRichard Peter Hill
Dec 12, 2012·Cancer Letters·Nicholas C D'AmatoJennifer K Richer
Mar 19, 2013·Cancer Letters·Jeffrey T Chang, Sendurai A Mani
Oct 11, 2011·Cell Stem Cell·Sebastian M DieterHanno Glimm
Oct 5, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Xiaojiao ChenYankai Xia
Nov 30, 2012·Cell Death & Disease·G ViticchièE Candi
Jun 29, 2013·Cell Death & Disease·J-I HanaiV P Sukhatme
Jun 8, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Laura Romero-PérezJosé Palacios
Feb 9, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Robert StraussJiri Bartek
Jun 12, 2013·Nature Biotechnology·Angera H Kuo, Michael F Clarke
Oct 5, 2010·Nature Cell Biology·Alberto Martin, Amparo Cano
Sep 8, 2010·Nature Cell Biology·Muh-Hwa YangKou-Juey Wu
Nov 22, 2011·Nature Medicine·Bogdan MateescuFatima Mechta-Grigoriou
Nov 10, 2013·Nature Medicine·Wai Leong Tam, Robert A Weinberg

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.