title: Up-regulated cten by FGF2 contributes to FGF2-mediated cell migration.
abstract: Cten is a focal adhesion molecule that is expressed at very low levels in most normal tissues. Nonetheless, its expression has been found to increase dramatically in many types of cancer including colorectal, breast, gastric, and pancreatic cancer, suggesting that cten may play a critical role during tumorigenesis. To study the mechanisms that induce cten expression and the function of up-regulated cten, we examined the effects of several cancer-associated growth factors and cytokines on cten expression. We found that EGF, FGF2, NGF, PDGF, TGF-β, IGF-1, IL-6, and IL-13 were able to induce cten expression in a dose- and time-dependent manner. The Mek-Erk and PI3K-Akt pathways were two main signaling cascades responsible for cten up-regulation, whereas the Jak-Stat pathway could contribute to the increase in some conditions. Since many of these factors are known to promote cell migration, we hypothesized that up-regulated cten might contribute to this process. This hypothesis was investigated in FGF2-mediated cell migration. Silencing of cten not only reduced regular cell motility but also FGF2-mediated cell migration. Overexpression of cten promoted cell migration and FGF2 treatment failed to further enhance cell migration. Our findings that (1) cten is a common downstream molecule of these cancer-associated growth factors and cytokines; and that (2) up-regulated cten modulates cell migration induced by FGF2 and likely other growth factors as well, strongly suggest that cten could be a potential downstream therapeutic target for treating cancers associated with aberrant signaling of these growth factors and cytokines.
authors.affiliation: Center for Tissue Regeneration and Repair, Department of Biochemistry and Molecular Medicine, University of California-Davis, Sacramento, California.
authors.forename: Shih-Ya
authors.initials: SY
authors.lastname: Hung
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Shih
authors.forename: Michelle
authors.initials: M
authors.lastname: Chen
authors.forename: Su Hao
authors.initials: SH
authors.lastname: Lo
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D000070876:Tensins; D015854:Up-Regulation
chemical_list: D008840:Microfilament Proteins; C000603371:TNS4 protein, human; D000070876:Tensins; D016222:Fibroblast Growth Factor 2
keywords: FGF2; cell migration; cten; focal adhesion