title: Role of the focal adhesion protein TRIM15 in colon cancer development.
abstract: The tripartite motif containing (TRIM) proteins are a large family of proteins that have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation, and signaling pathways. Here, we show that TRIM15 co-localized to focal adhesions through homo-dimerization and significantly suppressed cell migration. Domain mapping analysis indicated that B-box2 and PRY domains were essential for TRIM15 localization to focal adhesions and inhibition of cell migration. Our protein-protein interaction screen of TRIM15 with the integrin adhesome identified several TRIM15 interacting proteins including coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. TRIM15 expression was tissue-restricted and downregulated in colon cancer. Level of TRIM15 expression was associated with colon cancer cell migration, as well as both in vitro and in vivo tumor growth. These data provide novel insights into the role of TRIM15 as an additional component of the integrin adhesome, regulating cell migration, and suggest that TRIM15 may function as a tumor suppressor of colon cancer.
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea; Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Ok-Hee
authors.initials: OH
authors.lastname: Lee
authors.affiliation: Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Jinkyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Keun Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea; Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Woo
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea; Laboratory of Preventive Pharmacy, College of Pharmacy, Gachon University, Incheon, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Songyang
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea; Laboratory of Preventive Pharmacy, College of Pharmacy, Gachon University, Incheon, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea. Electronic address: youngsokchoi@cha.ac.kr.
authors.forename: Youngsok
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051356:Cortactin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013329:Structure-Activity Relationship
chemical_list: D000199:Actins; C495868:CTTN protein, human; D051356:Cortactin; D004268:DNA-Binding Proteins; C000597019:tripartite motif-containing protein 15, human
keywords: Cell migration; Colon cancer; Focal adhesion; TRIM15