Induction of integrin β3 by sustained ERK activity promotes the invasiveness of TGFβ-induced mesenchymal tumor cells

The emerging roles of integrin beta 3 in the epithelial mesenchymal transition (EMT) and drug resistance underline its significance in cancer metastasis and recurrence. However, the molecular mechanism underlying the distinctive expression of integrin beta 3 is less understood. In the present report, we demonstrated that repetitive exposure to transforming growth factor beta (TGF beta), a potent inducer of the EMT, significantly increased the expression of integrin beta 3 in A549 lung cancer cells with distinct mesenchymal properties, such as actin filament reorganization and invasiveness. Notably, integrin beta 3 expression was associated to cancer cell invasion and migration, and was determined not by Smad4-dependent pathways but by sustained ERK1/2 activity in the mesenchymal cancer cells. These data suggest that ERK1/2 plays an important role in mediating non-canonical TGF beta signal pathways for integrin beta 3 expression. Therefore, the targeting of the MEK/ERK activity seems to be a promising therapeutic approach to suppressing EMT-associated cancer progression that potentially occurs in TGF beta-enriched microenvironments, which would lead to the suppression of the metastatic potential of integrin beta 3-positive cancer cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.