The Integrin-Mediated ILK-Parvin-αPix Signaling Axis Controls Differentiation in Mammary Epithelial Cells

Epithelial cell adhesion to the surrounding extracellular matrix is necessary for their proper behavior and function. During pregnancy and lactation, mammary epithelial cells (MECs) receive signals from their interaction with laminin via beta 1-integrin (beta 1-itg) to establish apicobasal polarity and to differentiate in response to prolactin. Downstream of beta 1-itg, the scaffold protein Integrin Linked Kinase (ILK) has been identified as the key signal transducer that is required for both lactational differentiation and the establishment of apico-basal polarity. ILK is an adaptor protein that forms the IPP complex with PINCH and Parvins, which are central to its adaptor functions. However, it is not known how ILK and its interacting partners control tissue-specific gene expression. Expression of ILK mutants, which weaken the interaction between ILK and Parvin, revealed that Parvins have a role in mammary epithelial differentiation. This conclusion was supported by shRNA-mediated knockdown of the Parvins. In addition, shRNA knockdown of the Parvin-binding guanine nucleotide exchange factor alpha Pix prevented prolactin-induced differentiation. alpha Pix depletion did not disrupt focal adhesions, MEC proliferation, or polarity. This suggests that alpha Pix represents a differentiation-specific bifurcation point in beta 1-itg-ILK adhesive signaling. In summary, this study has identified a new role for Parvin and alpha Pix downstream of the integrin-ILK signaling axis for MEC differentiation. (C) 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.