Overexpression of T-cadherin (T-cad) transcripts occurs in approximately 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.
|Numero di pagine||11|
|Rivista||THE FASEB JOURNAL|
|Stato di pubblicazione||Published - 2006|
All Science Journal Classification (ASJC) codes
- Molecular Biology
Gentile, C., Chenailler, C., Riou, P., Saffroy, R., Piatier-Tonneau, D., Franc, B., Resink, T., Debuire, B., Lemoine, A., Rubinstein, E., & Gentile, C. (2006). Expression of T-cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma. THE FASEB JOURNAL, 20, 2291-2301.