Semaphorin 7a exerts pleiotropic effects to promote breast tumor progression

Abstract

Understanding what drives breast tumor progression is of utmost importance for blocking tumor metastasis; we have identified that semaphorin 7a is a potent driver of ductal carcinoma in situ (DCIS) progression. Semaphorin 7a is a GPI membrane anchored protein that promotes attachment and spreading in multiple cell types. Here we show that increased expression of SEMA7A occurs in a large percentage of breast cancers and is associated with decreased overall and distant metastasis free survival. In both in vitro and in vivo models, shRNA mediated silencing of SEMA7A reveals roles for semaphorin 7a in the promotion of DCIS growth, motility, and invasion as well as lymphangiogenesis in the tumor microenvironment. Our studies also uncover a relationship between COX-2 and semaphorin 7a expression and suggest that semaphorin 7a promotes tumor cell invasion on collagen and lymphangiogenesis via activation of β ₁-integrin receptor. Our results suggest that semaphorin 7a, may be novel target for blocking breast tumor progression.