TGFβ and matrix-regulated epithelial to mesenchymal transition.

Abstract

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 β (TGFβ) 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 TGFβ signaling can be detected in carcinoma and stromal cells, and TGFβ-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 TGFβ 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.

• Authors: Aristidis Moustakas, Paraskevi Heldin
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1840 Issue 8 Pg. 2621-34 (Aug 2014) ISSN: 0006-3002 [Print] Netherlands
• PMID: 24561266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014. Published by Elsevier B.V.

Chemical References

• Smad Proteins
• Transforming Growth Factor beta

Topics

• Animals
• Breast Neoplasms (genetics, pathology)
• Epithelial-Mesenchymal Transition (genetics)
• Extracellular Matrix (metabolism)
• Humans
• Neoplastic Stem Cells (metabolism, pathology)
• Smad Proteins (metabolism)
• Transforming Growth Factor beta (metabolism)