Tropomyosin3 overexpression and a potential link to epithelial-mesenchymal transition in human hepatocellular carcinoma

TPM3-siRNA was transfected into 2 HCC cell lines, HepG2 and SNU-475, which had shown overexpression of TPM3. Knockdown of TPM3 was verified by real-time qRT-PCR and western blotting targeting TPM3. Migration and invasion potentials were examined using transwell membrane assays. Cell growth capacity was examined by colony formation and soft agar assays.Silencing TPM3 resulted in significant suppression of migration and invasion capacities in both HCC cell lines. To elucidate the mechanisms behind suppressed migration and invasiveness, we examined expression levels of Snail and E-cadherin known to be related to epithelial-mesenchymal transition (EMT) after TPM3 knockdown. In the TPM3 knockdown cells, E-cadherin expression was significantly upregulated and Snail downregulated compared with negative control. TPM3 knockdown also inhibited colony formation and anchorage independent growth of HCC cells.Based on our findings, we formulate a hypothesis that overexpression of TPM3 activates Snail mediated EMT, which will repress E-cadherin expression and that it confers migration or invasion potentials to HCC cells during hepatocarcinogenesis. To our knowledge, this is the first evidence that TPM3 gets involved in migration and invasion of HCCs by modifying EMT pathway.Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer-related death in the world [1]. A number of studies have been suggesting the molecular mechanisms involved in hepatocarcinogenesis such as MAPK, EGFR, p53, Wnt, TGF-B, Ras and Rb pathways [2-5]. However, given that prognosis of the disease remains poor, it is still important to understand hepatocarcinogenesis mechanisms and to identify effective markers for early diagnosis and accurate prognostication which reflect biological phenomena well.In our recent study which reported the chromosomal alterations in HCC by genome-wide array-CGH analysis, we found that a 1q21.3 locus was recurrently amplified a