A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells
Ulrike Burk,Joerg Schubert,Ulrich F. Wellner,Otto Schmalhofer,Elizabeth Vincan,Simone Spaderna,Thomas Brabletz +6 more
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TLDR
Results indicate that ZEB1 triggers an microRNA‐mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells, and thus explain the strong intratumorous heterogeneity observed in many human cancers.Abstract:
The embryonic programme 'epithelial-mesenchymal transition' (EMT) is thought to promote malignant tumour progression. The transcriptional repressor zinc-finger E-box binding homeobox 1 (ZEB1) is a crucial inducer of EMT in various human tumours, and was recently shown to promote invasion and metastasis of tumour cells. Here, we report that ZEB1 directly suppresses transcription of microRNA-200 family members miR-141 and miR-200c, which strongly activate epithelial differentiation in pancreatic, colorectal and breast cancer cells. Notably, the EMT activators transforming growth factor beta2 and ZEB1 are the predominant targets downregulated by these microRNAs. These results indicate that ZEB1 triggers an microRNA-mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells. Alternatively, depending on the environmental trigger, this loop might switch and induce epithelial differentiation, and thus explain the strong intratumorous heterogeneity observed in many human cancers.read more
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MicroRNA in colorectal cancer: from benchtop to bedside
William K.K. Wu,Priscilla T. Y. Law,Chung W. Lee,Chi H. Cho,Daiming Fan,Kaichun Wu,Jun Yu,Joseph J.Y. Sung +7 more
TL;DR: With further insights into miRNA dysregulation in colon cancer and the advancement of RNA delivery technology, it is anticipated that novel miRNA-based therapeutics will emerge.
Journal ArticleDOI
The role of microRNAs in the regulation of cancer stem cells.
TL;DR: A better understanding of the modulation of CSC gene expression by miRNAs could aid the identification of promising biomarkers and therapeutic targets and may lead to the development of miRNA therapeutics specifically targeting CSCs.
Journal ArticleDOI
ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression.
Young Ho Ahn,Don L. Gibbons,Deepavali Chakravarti,Chad J. Creighton,Zain H. Rizvi,Henry P. Adams,Alexander Pertsemlidis,Philip A. Gregory,Josephine A. Wright,Gregory J. Goodall,Elsa R. Flores,Jonathan M. Kurie +11 more
TL;DR: Findings demonstrate that ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression and provide a compelling rationale to develop miR -34a as a therapeutic agent in lung cancer patients.
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Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells
Yoshihiro Takeyama,Mitsuo Sato,Mihoko Horio,Tetsunari Hase,Kenya Yoshida,Toshihiko Yokoyama,Harunori Nakashima,Naozumi Hashimoto,Yoshitaka Sekido,Adi F. Gazdar,John D. Minna,Masashi Kondo,Yoshinori Hasegawa +12 more
TL;DR: ZEB1 knockdown with RNA interference in three NSCLC cell lines with high ZEB1 expression suppressed to varying degrees mass culture growth and liquid colony formation but in all cases dramatically suppressed soft agar colony formation.
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A self-enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells.
Bogdan-Tiberius Preca,Bogdan-Tiberius Preca,Karolina Bajdak,Karolina Bajdak,Kerstin Mock,Kerstin Mock,Vignesh Sundararajan,Vignesh Sundararajan,Jessica Pfannstiel,Jochen Maurer,Jochen Maurer,Ulrich F. Wellner,Ulrich T. Hopt,Tilman Brummer,Tilman Brummer,Simone Brabletz,Simone Brabletz,Thomas Brabletz,Marc P. Stemmler,Marc P. Stemmler +19 more
TL;DR: A self‐enforcing feedback loop that employs CD44s to activate Z EB1 expression renders tumor cell stemness independent of external stimuli, as ZEB1 downregulates ESRP1, further promotingCD44s isoform synthesis.
References
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