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01-11-2009 | Brief Report

Autocrine semaphorin3A stimulates alpha2 beta1 integrin expression/function in breast tumor cells

Authors: Hongjie Pan, Luke S. Wanami, Thusitha R. Dissanayake, Robin E. Bachelder

Published in: Breast Cancer Research and Treatment | Issue 1/2009

Abstract

The axon repulsion factor semaphorin3A (SEMA3A) and its receptor neuropilin-1 (NP-1) are expressed in breast tumor cells, and function as suppressors of tumor cell migration. Based on the knowledge that both SEMA3A and the α2β1 integrin suppress breast tumor cell migration, we studied the impact of SEMA3A signaling on α2β1 integrin expression/function. The incubation of breast tumor cells with SEMA3A increased α2 and β1 integrin levels, and stimulated tumor cell adhesion to the α2β1-binding matrix protein collagen I. Conversely, reducing SEMA3A expression in breast tumor cells decreased α2β1 levels and collagen adhesion. The ability of SEMA3A to increase tumor cell adhesion to collagen was dependent on both the SEMA3A receptor NP-1 and the glycogen synthase kinase-3. The incubation of breast tumor cells with SEMA3A disrupted the actin cytoskeleton, and reduced both tumor cell migratory and invasive behavior. Importantly, using an α2β1-neutralizing antibody, we demonstrated that SEMA3A suppression of tumor cell migration is dependent on α2β1. Our studies indicate that expression of the α2β1 integrin, a suppressor of metastatic breast tumor growth, is stimulated in breast tumor cells by an autocrine SEMA3A pathway.

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Title: Autocrine semaphorin3A stimulates alpha2 beta1 integrin expression/function in breast tumor cells
Authors: Hongjie Pan
Luke S. Wanami
Thusitha R. Dissanayake
Robin E. Bachelder
Publication date: 01-11-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0179-y

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