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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs. Strathprints provides access to thousands of Open Access research papers by University of Strathclyde researchers, including those from the School of Psychological Sciences & Health - but also papers by researchers based within the Faculties of Science, Engineering, Humanities & Social Sciences, and from the Strathclyde Business School.

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IGFBP5 induces cell adhesion, increases cell survival and inhibits cell migration in MCF-7 human breast cancer cells

Sureshbabu, A and Okajima, H and Yamanaka, D and Tonner, E and Shastri, S and Maycock, J and Szymanowska, M and Shand, J and Takahashi, S-I and Beattie, J and Allan, G J and Flint, David (2012) IGFBP5 induces cell adhesion, increases cell survival and inhibits cell migration in MCF-7 human breast cancer cells. Journal of Cell Science, 125 (7). pp. 1693-1705.

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Abstract

Maintenance of tissue boundaries is crucial for control of metastasis. We describe a novel signalling pathway in which epithelial cell disruption can be minimised and thereby restricts epithelial-mesenchymal transgressions. This involves IGFBP-5 release from apoptotic cells, which increases epithelial cell adhesion on mesenchymal but not epithelial ECM and involves direct interaction of IGFBP-5 with α2β1 integrins. IGFBP-5 also induced adhesion to vitronectin in the absence of αVβ3 integrin, the vitronectin receptor, again via an α2β1 integrin-dependent action, suggesting that IGFBP-5 can induce spreading on matrices, even in the absence of the integrins normally used. Using IGFBP-5 mutants we demonstrate that the effect is IGF-independent but requires the heparin-binding domain in the c-terminus of IGFBP-5. A truncated c-terminal mutant of IGFBP-5 also induced adhesion. Adhesion induced by IGFBP-5 was cdc42-dependent and resulted in activation of ILK and Akt. Consistent with these changes, IGFBP-5 facilitated prolonged cell survival in nutrient-poor conditions and decreased phosphorylation of the stress-activated kinase p38MAPK. Whilst IGFBP-5 enhanced adhesion, it inhibited cell migration although this was not evident using the truncated c-terminal mutant, suggesting that effects of IGFBP-5 on adhesion and migration involve different mechanisms. These responses to IGFBP-5 would be anticipated to reduce metastatic potential.