Abstract

Abstract The tazarotene-induced gene 1 (TIG1), also known as retinoic acid receptor responder 1 (RARRES1), is a putative tumor suppressor gene. The gene encodes a carboxypeptidase inhibitor for ATP/GTP binding protein-like 2 (AGBL2). This study identified TIG1 binding proteins and characterized the activities of TIG1 on cellular invasion of HCT116 colon cancer cells stimulated by the cathepsin L2 (CTSL2). The cytoplasmic portion of the TIG1A isoform was used for identification of TIG1 binding proteins using the yeast two-hybrid screening, and six genes, CTSL2, DNAJC8, SPATA22, SPINK2, VAC14, and C6orf225, were selected. CTSL2, a cysteine protease with an increased expression shown in breast and colon carcinomas, was selected for analysis. Immunoprecipitation analysis using transiently transfected cytosols confirmed the binding between both TIG1 isoforms and CTSL2. Both TIG1A and CTSL2 were secreted proteins; however, the interaction of both proteins in culture supernatants was not detected. Further immunoprecipitation analysis using purified recombinant proteins demonstrated direct binding between both TIG1 isoforms and CTSL2. Cellular invasion of HCT116 cells was increased by 52 to 71% in CTSL2 transiently transfected cells. Both TIG1 isoforms had no effects on cellular invasion of HCT116 cells. However, TIG1A and TIG1B significantly inhibited CTSL2-stimulated cellular invasion by 65.1 and 62.9%, respectively. In conclusion, both TIG1 isoforms interact with CTSL2 and inhibited CTSL2-stimulated cellular invasion of HCT116 cells. The results suggest that TIG1 may suppress CTSL2-mediated cellular invasion through inhibiting the activation of CTSL2 protease, and merit for further investigation. 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 501. doi:1538-7445.AM2012-501

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