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Transmembrane 4 L six family member 5 (TM4SF5) enhances migration and invasion of hepatocytes for effective metastasis
Authors:Sin‐Ae Lee  Tae You Kim  Tae Kyoung Kwak  Hyeonjung Kim  Semi Kim  Hyo Jeong Lee  Sung‐Hoon Kim  Ki Hun Park  Hyun Jeong Kim  Moonjae Cho  Jung Weon Lee
Institution:1. Cancer Research Institute, Seoul National University, Seoul 110‐799, Korea;2. Department of Molecular & Clinical Oncology, College of Medicine, Seoul National University, Seoul 110‐799, Korea;3. Department of Tumor Biology, College of Medicine, Seoul National University, Seoul 110‐799, Korea;4. KRIBB, Taejon 305‐333, Korea;5. CPMDRC, College of Oriental Medicine, Kyunghee University, Seoul 131‐701, Korea;6. Division of Applied Life Science, EB‐NCRC, Gyeongsang National University, Jinju 660‐701, Korea;7. Department of Dental Anesthesiology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110‐799, Korea;8. Department of Medicine, Cheju National University, Jeju 690‐756, Korea;9. Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Cell Dynamics Research Center, Seoul National University, Seoul 151‐742, Korea
Abstract:Overexpression of transmembrane 4 L six family member 5 (TM4SF5), a four‐transmembrane L6 family member, causes aberrant cell proliferation and angiogenesis, but the roles of TM4SF5 in migration, invasion, and tumor metastasis remain unknown. Using in vitro hepatocarcinoma cells that ectopically or endogenously express TM4SF5 and in vivo mouse systems, roles of TM4SF5 in metastatic potentials were examined. We found that TM4SF5 expression facilitated migration, invadopodia formation, MMP activation, invasion, and eventually lung metastasis in nude mice, but suppression of TM4SF5 with its shRNA blocked the effects. Altogether, TM4SF5‐mediated migration and invasion suggest that TM4SF5 may be therapeutically targeted to deal with TM4SF5‐mediated hepatocellular cancers. J. Cell. Biochem. 111: 59–66, 2010. © 2010 Wiley‐Liss, Inc.
Keywords:invadopodia  migration  invasion  TM4SF5  MMP  metastasis
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