TGFβ, Fibronectin and Integrin α5β1 Promote Invasion in Basal Cell Carcinoma

The Journal of Investigative Dermatology
François KuonenOlivier Gaide

Abstract

Basal cell carcinoma (BCC) is the most frequent human cancer and is becoming an important health problem in an aging population. Based on their clinical and histological characteristics, thick BCC are typically divided into low-risk nodular and high-risk infiltrative subtypes, although the underlying mechanisms are poorly understood. We have identified molecular mechanisms that explain the aggressiveness of high-risk infiltrative BCC, with a potential direct clinical impact. In this study, we first show that fibroblasts, transforming growth factor-β, and fibronectin are found preferentially in infiltrative human BCC. This allowed us to develop in vivo models for the study of infiltrative BCC, which in turn let us confirm the role of transforming growth factor-β in inducing peritumoral fibronectin deposition and tumor infiltration. We then show that fibronectin promotes adhesion and migration of BCC cell lines through integrin α5β1-mediated phosphorylation of focal adhesion kinase. Fittingly, both inhibition of integrin α5β1 and phospho-focal adhesion kinase prevent fibronectin-induced migration of BCC cells in vitro as well as BCC infiltration in vivo. Altogether, our results open important insights into the pathogenesis of agg...Continue Reading

Citations

Feb 16, 2019·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·A Sue MenkoMary Ann Stepp
Dec 22, 2019·Cells·Tsung-Cheng LinHung-Chi Cheng
Dec 16, 2018·Journal of Tissue Engineering and Regenerative Medicine·Jan Philipp KrügerMichaela Endres
Dec 29, 2020·The Journal of Investigative Dermatology·Yao Ke, Xiao-Jing Wang
Jan 8, 2021·OncoTargets and Therapy·Jianbing HouHongjuan Cui
Apr 19, 2021·The Journal of Investigative Dermatology·Rehan VillaniKiarash Khosrotehrani
Oct 6, 2021·Cell Reports·François KuonenAnthony E Oro

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