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

Nicholas Rooney, Pengbo Wang, Keith Brennan, Andrew Gilmore, Charles Streuli

Research output: Contribution to journalArticlepeer-review


Epithelial cell adhesion to the surrounding extracellular matrix is necessary for their proper behaviour 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 signalling. In summary, this study has identified a new role for Parvin and αPix downstream of the integrin-ILK signalling axis for MEC differentiation.
Original languageEnglish
Pages (from-to)2408-2417
JournalJournal of Cellular Physiology
Issue number11
Early online date27 Mar 2016
Publication statusPublished - 2016

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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