title: The Tensin-3 protein, including its SH2 domain, is phosphorylated by Src and contributes to tumorigenesis and metastasis.
abstract: In cell lines from advanced lung cancer, breast cancer, and melanoma, endogenous tensin-3 contributes to cell migration, anchorage-independent growth, and tumorigenesis. Although SH2 domains have not been reported previously to be phosphorylated, the tensin-3 SH2 domain is a physiologic substrate for Src. Tyrosines in the SH2 domain contribute to the biological activity of tensin-3, and phosphorylation of these tyrosines can regulate ligand binding. In a mouse breast cancer model, tensin-3 tyrosines are phosphorylated in a Src-associated manner in primary tumors, and experimental metastases induced by tumor-derived cell lines depend on endogenous tensin-3. Thus, tensin-3 is implicated as an oncoprotein regulated by Src and possessing an SH2 domain with a previously undescribed mechanism for the regulation of ligand binding.
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Qian
authors.forename: Guorong
authors.initials: G
authors.lastname: Li
authors.forename: William C
authors.initials: WC
authors.lastname: Vass
authors.forename: Alex
authors.initials: A
authors.lastname: Papageorge
authors.forename: Renard C
authors.initials: RC
authors.lastname: Walker
authors.forename: Laura
authors.initials: L
authors.lastname: Asnaghi
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Steinbach
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
authors.forename: Kent
authors.initials: K
authors.lastname: Hunter
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000209:etiology*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D000070876:Tensins; D014162:Transfection; D018909:src Homology Domains
chemical_list: D034741:RNA, Small Interfering; D000070876:Tensins; D010749:Phosphoprotein Phosphatases; C500779:Tns3 protein, mouse