Change search
ReferencesLink to record
Permanent link

Direct link
APC and Smad7 link TGF beta type I receptors to the microtubule system to promote cell migration
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. (Uppsala Univ, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden and Jilin Univ, Sch Stomatol, Changchun 130041, Peoples R China)
Show others and affiliations
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
Abstract [en]

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
American Society of Cell Biology, USA , 2012. Vol. 23, no 11, 2109-2121 p.
Keyword [en]
National Category
Cancer and Oncology
URN: urn:nbn:se:umu:diva-57614DOI: 10.1091/mbc.E10-12-1000ISI: 000306286400008OAI: diva2:543488
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2012-08-08Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Mu, YabingLandström, Marene
By organisation
In the same journal
Molecular Biology of the Cell
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 78 hits
ReferencesLink to record
Permanent link

Direct link