title: 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 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.
authors.affiliation: Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Black
authors.affiliation: Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Nelson
authors.affiliation: Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.|University of Colorado Cancer Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Gurule
authors.affiliation: The University of Arizona Cancer Center, The University of Arizona, Tucson, AZ, USA.|Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Futscher
authors.affiliation: Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.|University of Colorado Cancer Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.|University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Lyons
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D058851:GPI-Linked Proteins / Q000008:administration & dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D058685:Genetic Pleiotropy; D006801:Humans; D042583:Lymphangiogenesis / Q000235:genetics; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology; D051379:Mice; D039961:Semaphorins / Q000008:administration & dosage / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; C118753:SEMA7A protein, human; D039961:Semaphorins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human