title: The Integrin-Mediated ILK-Parvin-αPix Signaling Axis Controls Differentiation in Mammary Epithelial Cells.
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 Wiley Periodicals, Inc.
authors.affiliation: The Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rooney
authors.affiliation: The Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Wang
authors.affiliation: The Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Brennan
authors.affiliation: The Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Gilmore
authors.affiliation: The Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Streuli
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D019012:Integrin beta1 / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011388:Prolactin / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000099200:Scaffold Protein ILK
chemical_list: D019012:Integrin beta1; D008840:Microfilament Proteins; D011388:Prolactin; D017346:Protein Serine-Threonine Kinases; D064067:Rho Guanine Nucleotide Exchange Factors; D000099200:Scaffold Protein ILK; C576604:Arhgef6 protein, mouse; C519774:Parva protein, mouse