Abstract
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 β1‐integrin (β1‐itg) to establish apico‐basal polarity and to differentiate in response to prolactin. Downstream of β1‐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 αPix prevented prolactin‐induced differentiation. αPix depletion did not disrupt focal adhesions, MEC proliferation, or polarity. This suggests that αPix represents a differentiation‐specific bifurcation point in β1‐itg‐ILK adhesive signaling. In summary, this study has identified a new role for Parvin and αPix downstream of the integrin‐ILK signaling axis for MEC differentiation. J. Cell. Physiol. 231: 2408–2417, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
Highlights
Epithelial cell adhesion to the surrounding extracellular matrix is necessary for their proper behavior and function
Parvins have a role in mammary epithelial cell differentiation
In order to study the role of Integrin Linked Kinase (ILK)-regulated proteins in the control of Prl-driven differentiation, we used the mouse mammary epithelial cells (MECs) cell line EpH4, which was originally isolated from mid-pregnant mice (Fialka et al, 1996)
Summary
Epithelial cell adhesion to the surrounding extracellular matrix is necessary for their proper behavior and function. Mammary epithelial cells (MECs) receive signals from their interaction with laminin via b1-integrin (b1-itg) to establish apicobasal polarity and to differentiate in response to prolactin. ILK is an adaptor protein that forms the IPP complex with PINCH and Parvins, which are central to its adaptor functions It is not known how ILK and its interacting partners control tissue-specific gene expression. In the mammary gland, analysis of ILK-null MECs showed that polarized acini failed to form, lactation was reduced, and in vivo pups were undersized and malnourished (Akhtar et al, 2009; Akhtar and Streuli, 2013) It is not known what ILK associates with in order to transmit the adhesive cues from b1-itg that are necessary for epithelial differentiation. Our data suggest that the ILK-Parvin-Pix signaling axis is important for tissue-specific gene expression in the mammary gland
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