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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Overexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A.
Sul Ki Choi,Sul Ki Choi,Hoe Suk Kim,Tiefeng Jin,Eun Hye Hwang,Minji Jung,Woo Kyung Moon,Woo Kyung Moon +7 more
TL;DR: The data demonstrate a mechanism in which the miR-141/200c cluster, through FAK- and PI3K/AKT-mediated signaling by means of increased VEGF-A secretion, promotes the migratory and invasive abilities of MDA-MB-231 cells.
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COX-2 Elevates Oncogenic miR-526b in Breast Cancer by EP4 Activation
TL;DR: Novel findings are presented that miRNA 526b is a COX-2 upregulated, oncogenic miRNA promoting SLCs, the expression of which follows EP4 receptor-mediated signaling, and is a promising biomarker for monitoring and personalizing breast cancer therapy.
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Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer
Emi Tokuda,Toshiki Itoh,Junya Hasegawa,Takeshi Ijuin,Yukiko Takeuchi,Yasuhiro Irino,Miki Fukumoto,Tadaomi Takenawa +7 more
TL;DR: This study shows that changes in cell-cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate in the Golgi apparatus in breast cancer cells, and provides a new model for breast cancer cell progression in which progression is controlled by PI(4)P levels in the golgi apparatus.
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The microRNA-200/Zeb1 axis regulates ECM-dependent β1-integrin/FAK signaling, cancer cell invasion and metastasis through CRKL.
Christin Ungewiss,Zain H. Rizvi,Jonathon D. Roybal,David H. Peng,Kathryn A. Gold,Dong Hoon Shin,Chad J. Creighton,Don L. Gibbons +7 more
TL;DR: It is demonstrated that CRKL serves as an adaptor molecule to facilitate focal adhesion formation, mediates outside-in signaling through Itgβ1 to drive cell invasion, and inside-out signaling that maintains tumor cell-matrix contacts required for cell invasion.
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The role of microRNAs in different types of thyroid carcinoma: a comprehensive analysis to find new miRNA supplementary therapies.
TL;DR: The available data on miRNA dysregulation in different thyroid tumors including papillary, follicular, anaplastic, and medullary thyroid carcinomas are reviewed aiming to introduce the last updates in miRNAs-thyroid cancer relation.
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