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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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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Epithelial-Mesenchymal Transitions in Development and Disease
Jean Paul Thiery,Jean Paul Thiery,Hervé Acloque,Ruby Yun-Ju Huang,Ruby Yun-Ju Huang,M. Angela Nieto +5 more
TL;DR: The mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
TL;DR: Recent advances in the understanding of miRNAs in cancer and in other diseases are described and the challenge of identifying the most efficacious therapeutic candidates is discussed and a perspective on achieving safe and targeted delivery of miRNA therapeutics is provided.
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EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer
TL;DR: This review will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs, and highlight recent studies implicating the function of TGF-β-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal.
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Regulatory networks defining EMT during cancer initiation and progression
Bram De Craene,Geert Berx +1 more
TL;DR: The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them.
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MicroRNAs in cancer.
TL;DR: In this paper, the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies are discussed.
References
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TL;DR: Key features of EMT are outlined, evidence for its involvement in the dissemination of tumours is discussed and the mechanisms that regulate EMT in the tumour context are reviewed, with a particular focus on breast cancer.
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Samir Attoub,Veerle Noë,Luciano Pirola,Erik Bruyneel,Eric Chastre,Marc Mareel,Matthias P. Wymann,Christian Gespach +7 more
TL;DR: It is indicated that leptin may exert a local and beneficial effect on migration of normal colonic epithelial cells and reparation of the inflamed or wounded digestive mucosa, linking the nutritional and body fat status to digestive cancer susceptibility by stimulating the invasive capacity of colonichelial cells at early stages of neoplasia.
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SNAI1 is required for tumor growth and lymph node metastasis of human breast carcinoma MDA-MB-231 cells
TL;DR: Evidence of a major role for SNAI1 in both primary tumor growth and metastasis of human breast carcinoma MDA-MB-231 cells is provided and analysis of cell lines derived from lymph node metastasis indicates that SNAi1 expression is required for metastatic dissemination.
Journal Article
Expression of the Invasion Factor Laminin γ2 in Colorectal Carcinomas Is Regulated by β-Catenin
TL;DR: It is concluded that laminin-5 γ2 is another important target gene of nuclear β-catenin during tumor progression, which together with T-cell factor-DNA-binding proteins functions as transcriptional activator of genes involved in tumor progression.
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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
Thomas Brabletz,Simone Spaderna,Jochen Kolb,Falk Hlubek,Gerhard Faller,Christiane Bruns,Andreas Jung,Jens Nentwich,Isabelle Duluc,Claire Domon-Dell,Thomas Kirchner,Jean-Noël Freund +11 more
TL;DR: Cell culture experiments show that collagen type I triggers a transient transcriptional down-regulation of Cdx2 and its intestine-specific target gene sucrase isomaltase, associated with a loss of differentiation, indicating an active role for the tumor environment in malignant tumor progression.