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Expression of T‐cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma
Author(s) -
Riou Philippe,
Saffroy Raphael,
Chenailler Catherine,
Franc Brigitte,
Gentile Carla,
Rubinstein Eric,
Resink Therese,
Debuire Brigitte,
PiatierTonneau Dominique,
Lemoine Antoinette
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6085com
Subject(s) - gene silencing , matrigel , cadherin , biology , cancer research , hepatocellular carcinoma , metastasis , hccs , motility , cell , angiogenesis , cancer , microbiology and biotechnology , gene , biochemistry , genetics
Overexpression of T‐cadherin (T‐cad) transcripts occurs in ≈50% of human hepatocellular carcinomas (HCCs). To elucidate T‐cad functions in HCC, we examined T‐cad protein expression in normal and tumoral human livers and hepatoma cell lines and investigated its influence on invasive potential of HCC using RNA interference silencing of T‐cad expression in Mahlavu cells. Whereas T‐cad expression was restricted to endothelial cells (EC) from large blood vessels in normal livers, it was up‐regulated in sinusoidal EC from 8/15 invasive HCCs. Importantly, in three of them (38%) T‐cad was detected in tumor cells within regions in which E‐cadherin expression was absent. Among six hepatoma cell lines, only Mahlavu expressed T‐cad but not E‐cadherin. T‐cad exhibited a globally punctuate distribution in quiescent Mahlavu and additionally it concentrated at the leading edge of migrating cells. Matrigel invasion assay revealed that Mahlavu possess a high invasive potential that was significantly inhibited by T‐cad silencing. Wound healing and random motility assays demonstrated that inhibition of T‐cad expression in Mahlavu significantly reduced their motility. We propose that T‐cad expression in tumor cells might occur by cadherin‐switching during epithelial‐mesenchymal transition and may represent an additional mechanism contributing to HCC metastasis.—Riou, P., Saffroy, R., Chenailler, C., Franc, B., Gentile, C., Rubinstein, E., Resink, T., Debuire, B., Piatier‐Tonneau, D., Lemoine, A. Expression of T‐cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma. FASEB J. 20, 2291–2301 (2006)