| First Author | Ekman M | Year | 2012 |
| Journal | Mol Biol Cell | Volume | 23 |
| Issue | 11 | Pages | 2109-21 |
| PubMed ID | 22496417 | Mgi Jnum | J:197786 |
| Mgi Id | MGI:5494532 | Doi | 10.1091/mbc.E10-12-1000 |
| Citation | Ekman M, et al. (2012) APC and Smad7 link TGFbeta type I receptors to the microtubule system to promote cell migration. Mol Biol Cell 23(11):2109-21 |
| abstractText | 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 3beta (GSK-3beta). 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 (TGFbeta) and is known to inhibit various TGFbeta-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 TGFbeta stimulation. In addition, Smad7 forms a complex with APC and acts as an adaptor protein for p38 and GSK-3beta kinases to facilitate local TGFbeta/p38-dependent inactivation of GSK-3beta, 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 TGFbeta type I receptor to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFbeta. |
