Semaphorin 7a exerts pleiotropic effects to promote breast tumor progression

• DOI: 10.1038/onc.2016.49
• Publication Date: 2016-04-11T13:43:16Z
• Authors: S A Black; A C Nelson; N J Gurule; B W Futscher; T R Lyons
• Keywords: Lymphangiogenesis; Tumor progression; Plexin; Neuropilin

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 glycophosphatidylinositol 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, short hairpin-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 β1-integrin receptor. Our results suggest that semaphorin 7a may be novel target for blocking breast tumor progression.