Cross-Talk between the TGF-β and Cell Adhesion Signaling Pathways in Cancer.

Abstract

Transforming growth factor-β (TGF-β) is strongly associated with the cell adhesion signaling pathway in cell differentiation, migration, etc. Mechanistically, TGF-β is secreted in an inactive form and localizes to the extracellular matrix (ECM) via the latent TGF-β binding protein (LTBP). However, it is the release of mature TGF-β that is essential for the activation of the TGF-β signaling pathway. This progress requires specific integrins (one of the main groups of cell adhesion molecules (CAMs)) to recognize and activate the dormant TGF-β. In addition, TGF-β regulates cell adhesion ability through modulating CAMs expression. The aberrant activation of the TGF-β signaling pathway, caused by abnormal expression of key regulatory molecules (such as Smad proteins, certain transcription factors, and non-coding RNAs), promotes tumor invasive and metastasis ability via epithelial-mesenchymal transition (EMT) during the late stages of tumorigenesis. In this paper, we summarize the crosstalk between TGF-β and cell adhesion signaling pathway in cancer and its underlying molecular mechanisms.