Integrin ?3?1 Represses Reelin Expression in Breast Cancer Cells to Promote Invasion.
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ABSTRACT: Integrin ?3?1, a cell adhesion receptor for certain laminins, is known to promote breast tumor growth and invasion. Our previous gene microarray study showed that the RELN gene, which encodes the extracellular glycoprotein Reelin, was upregulated in ?3?1-deficient (i.e., ?3 knockdown) MDA-MB-231 cells. In breast cancer, reduced RELN expression is associated with increased invasion and poor prognosis. In this study we demonstrate that ?3?1 represses RELN expression to enhance breast cancer cell invasion. RELN mRNA was significantly increased upon RNAi-mediated ?3 knockdown in two triple-negative breast cancer cell lines, MDA-MB-231 and SUM159. Modulation of baseline Reelin levels altered invasive potential, where enhanced Reelin expression in MDA-MB-231 cells reduced invasion, while RNAi-mediated suppression of Reelin in SUM159 cells increased invasion. Moreover, treatment of ?3?1-expressing MDA-MB-231 cells with culture medium that was conditioned by ?3 knockdown MDA-MB-231 cells led to decreased invasion. RNAi-mediated suppression of Reelin in ?3 knockdown MDA-MB-231 cells mitigated this effect of conditioned-medium, identifying secreted Reelin as an inhibitor of cell invasion. These results demonstrate a novel role for ?3?1 in repressing Reelin in breast cancer cells to promote invasion, supporting this integrin as a potential therapeutic target.
SUBMITTER: Ndoye A
PROVIDER: S-EPMC7832892 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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