期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms6937
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资金
- INSERM
- Association pour la Recherche sur le Cancer (ARC)
- National Institutes of Health (NIH) [R01, DK074398, DK091530]
- National Breast Cancer Foundation (NBCF), Australia
- UK Biotechnology and Biological Sciences Research Council [BB/I007806/1]
- Cancer Research UK [C23338/A15965]
- Cancer Research UK [15965] Funding Source: researchfish
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK067153, R01DK091530, R01DK074398] Funding Source: NIH RePORTER
Signalling triggered by adhesion to the extracellular matrix plays a key role in the spatial orientation of epithelial polarity and formation of lumens in glandular tissues. Phosphoinositide 3-kinase signalling in particular is known to influence the polarization process during epithelial cell morphogenesis. Here, using Madin-Darby canine kidney epithelial cells grown in 3D culture, we show that the p110 delta isoform of phosphoinositide 3-kinase co-localizes with focal adhesion proteins at the basal surface of polarized cells. Pharmacological, siRNA-or kinase-dead-mediated inhibition of p110 delta impair the early stages of lumen formation, resulting in inverted polarized cysts, with no laminin or type IV collagen assembly at cell/extracellular matrix contacts. p110 delta also regulates the organization of focal adhesions and membrane localization of dystroglycan. Thus, we uncover a previously unrecognized role for p110 delta in epithelial cells in the orientation of the apico-basal axis and lumen formation.
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