Abstract 1086: Discoidin domain receptor 1 contributes to tumorigenesis through modulation of TGFBI expression

Discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family. It is activated by binding to its ligand, collagen and plays a key role in cell survival, adhesion, migration and invasion. Although DDR1 is present in several normal tissues, it is overexpressed in various cancer types, including lung, colon, ovary and breast tumors as well as in gliomas, where it is known to be associated with poor prognosis. The significance of DDR1 in cancer was illustrated using shRNA silencing, which impaired tumor cell growth, both in vitro and in vivo. Using microarray analysis of tumor cells with DDR1 knockdown, we identified an upregulation of TGFBI expression, which was subsequently confirmed at the protein level. TGFBI is a TGFβ induced extracellular matrix protein secreted by tumor cells and has been reported to act as either a tumor promoter or suppressor, depending upon tumor type. Exogenous addition of recombinant TGFBI to tumor cells inhibited clonogenic growth, recapitulating shRNA data. When grown in vivo as xenografts, the DDR1 knockdown cell lines demonstrated a similar phenotype of reduced growth and tumors exhibited an increase in TGFBI protein levels. In summary, our data suggests that DDR1 expression levels influences tumor growth in part through modulation of TGFBI expression. Ongoing studies will help to understand how DDR1 and TGFBI are linked and contribute to tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1086. doi:1538-7445.AM2012-1086