APC and Smad7 link the TGFβ type I receptors to the microtubule system to promote cell migration
2012 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 23, no 11, 2109-2121 p.Article in journal (Refereed) Published
Cell migration occurs by activation of complex regulatory pathways that are spatially and temporally integrated in response to extracellular cues. Binding of adenomatous polyposis coli (APC) to the microtubule plus ends in polarized cells is regulated by glycogen synthase kinase 3 beta (GSK-3 beta). This event is crucial for establishment of cell polarity during directional migration. However, the role of APC for cellular extension in response to extracellular signals is less clear. Smad7 is a direct target gene for transforming growth factor-beta (TGF beta) and is known to inhibit various TGF beta-induced responses. Here we report a new function for Smad7. We show that Smad7 and p38 mitogen-activated protein kinase together regulate the expression of APC and cell migration in prostate cancer cells in response to TGF beta stimulation. In addition, Smad7 forms a complex with APC and acts as an adaptor protein for p38 and GSK-3 beta kinases to facilitate local TGF beta/p38-dependent inactivation of GSK-3 beta, accumulation of beta-catenin, and recruitment of APC to the microtubule plus end in the leading edge of migrating prostate cancer cells. Moreover, the Smad7-APC complex links the TGF beta type I receptor to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGF beta.
Place, publisher, year, edition, pages
2012. Vol. 23, no 11, 2109-2121 p.
APC, Smad7, GSK-3beta, p38, TGF-beta, cell migration
Medical and Health Sciences
Research subject Cell Research
IdentifiersURN: urn:nbn:se:uu:diva-159146DOI: 10.1091/mbc.E10-12-1000ISI: 000306286400008OAI: oai:DiVA.org:uu-159146DiVA: diva2:442784