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TGF beta and matrix-regulated epithelial to mesenchymal transition
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Science for Life Laboratory, SciLifeLab.
2014 (English)In: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1840, no 8, 2621-2634 p.Article, review/survey (Refereed) Published
Abstract [en]

Background: The progression of cancer through stages that guide a benign hyperplastic epithelial tissue towards a fully malignant and metastatic carcinoma, is driven by genetic and microenvironmental factors that remodel the tissue architecture. The concept of epithelial-mesenchymal transition (EMT) has evolved to emphasize the importance of plastic changes in tissue architecture, and the cross-communication of tumor cells with various cells in the stroma and with specific molecules in the extracellular matrix (ECM). Scope of the review: Among the multitude of ECM-embedded cytokines and the regulatory potential of ECM molecules, this article focuses on the cytokine transforming growth factor p (TOM) and the glycosaminoglycan hyaluronan, and their roles in cancer biology and EMT. For brevity, we concentrate our effort on breast cancer. Major conclusions: Both normal and abnormal TGF beta, signaling can be detected in carcinoma and stromal cells, and TGF beta-induced EMT requires the expression of hyaluronan synthase 2 (HAS2). Correspondingly, hyaluronan is a major constituent of tumor ECM and aberrant levels of both hyaluronan and TGF beta are thought to promote a wounding reaction to the local tissue homeostasis. The link between EMT and metastasis also involves the mesenchymal epithelial transition (MET). ECM components, signaling networks, regulatory non-coding RNAs and epigenetic mechanisms form the network of regulation during EMT-MET. General significance: Understanding the mechanism that controls epithelial plasticity in the mammary gland promises the development of valuable biomarkers for the prognosis of breast cancer progression and even provides new ideas for a more integrative therapeutic approach against disease. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. (C) 2014 The Authors. Published by Elsevier B.V.

Place, publisher, year, edition, pages
2014. Vol. 1840, no 8, 2621-2634 p.
Keyword [en]
Epithelial-mesenchymal transition, Hyaluronan, Proteoglycan, Signal transduction, Transforming growth factor beta, Tumor invasiveness
National Category
Biochemistry and Molecular Biology Biophysics
Identifiers
URN: urn:nbn:se:uu:diva-230238DOI: 10.1016/j.bbagen.2014.02.004ISI: 000339035400024OAI: oai:DiVA.org:uu-230238DiVA: diva2:739807
Available from: 2014-08-21 Created: 2014-08-21 Last updated: 2017-12-05Bibliographically approved

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Moustakas, AristidisHeldin, Paraskevi

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