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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Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells.
Lukas Vrba,Taylor J. Jensen,James C. Garbe,Ronald L. Heimark,Anne E. Cress,Sally E. Dickinson,Martha R. Stampfer,Martha R. Stampfer,Bernard W. Futscher +8 more
TL;DR: It is reported that DNA methylation plays a role in the normal cell type-specific expression ofmiR-200c and miR-141 and this role appears evolutionarily conserved, since similar results were obtained in mouse.
Journal ArticleDOI
LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer.
TL;DR: Findings suggest that lncRNA-ATB, a mediator of TGF-β signaling, could predispose breast cancer patients to EMT and trastuzumab resistance.
Journal ArticleDOI
MiR-1 and miR-200 inhibit EMT via Slug -dependent and tumorigenesis via Slug -independent mechanisms
Yen-Nien Liu,Juan Juan Yin,Wassim Abou-Kheir,Paul G. Hynes,Orla Casey,Lei Fang,Ming Yi,Robert M. Stephens,Victoria Seng,Heather Sheppard-Tillman,Philip Martin,Philip Martin,Kathleen Kelly +12 more
TL;DR: The findings suggest that miR-1 has roles in regulating EMT and mesenchymal differentiation through Slug and functions in tumor-suppressive programs by regulating additional targets.
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Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer.
Yuji Toiyama,Keun Hur,Koji Tanaka,Yasuhiro Inoue,Masato Kusunoki,Clement Richard Boland,Ajay Goel +6 more
TL;DR: Serum miR-200c has strong potential to serve as a noninvasive biomarker for CRC prognosis and predicting metastasis and emerged as an independent prognostic marker for CRC.
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EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells
Carmen S. Tellez,Daniel E. Juri,Kieu Do,Amanda M. Bernauer,Cindy L. Thomas,Leah A. Damiani,Mathewos Tessema,Shuguang Leng,Steven A. Belinsky +8 more
TL;DR: It is shown that a 4-week exposure of immortalized human bronchial epithelial cells (HBEC) to tobacco carcinogens can induce a persistent, irreversible, and multifaceted dedifferentiation program marked by EMT and the emergence of stem cell-like properties.
References
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