Anoikis resistance in mammary epithelial cells is mediated by semaphorin 7a Semaphorin-7A and anoikis resistance

Abstract

Semaphorin-7a (SEMA7A), best known as a neuroimmune molecule, plays a diverse role in many cellular processes and pathologies. Here, we show that SEMA7A promotes anoikis resistance in cultured mammary epithelial cells through integrin mediated activation of pro-survival kinase AKT, which led us to investigate a role for SEMA7A during postpartum mammary gland involution- a normal process in development where cells die by anoikis. Our results reveal that SEMA7A is expressed on live mammary epithelial cells during involution, that SEMA7A expression is primarily observed in a6-integrin expressing cells, and that luminal progenitor cells, specifically, are decreased in mammary glands of SEMA7A-/- mice during involution. We further identify a SEMA7A/b1-integrin dependent mechanism of cell survival that promotes anoikis resistance, mammosphere formation, and chemoresistance in mammary epithelial cells and suggest that this mechanism is relevant for recurrence in breast cancer patients.