Abstract 3429: Mesenchymal hepatocellular carcinoma cells acquire cancer stem cell characteristics through Snail1

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality and the incidence of HCC is rising in the United States. Cancer stem cells (CSCs) are a subset of neoplastic cells that possess distinct survival mechanisms and plasticity crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by Transforming Growth Factor-β (TGF-β) has been linked to the acquisition of CSC characteristics in breast cancer. In patients with HCC, either a CSC or EMT phenotype correlates with a worse prognosis. In this report, we aim to link EMT to CSCs and to further elucidate the mechanism by which cells acquire CSC characteristics during EMT. We utilized human (Huh7, MHCC97-L) and murine (P2E, P2M; Ding et al Hepatology. 2010) liver cancer cell lines, and analysis included gene and protein expression, FACS, migration and invasion assays, and chemotherapy resistance assay. Human mesenchymal MHCC97 cells demonstrate decreased E-cadherin, increased Snail1, and enhanced migration and invasion compared to epithelial Huh7 cells. MHCC97 cells demonstrate significant upregulation of stem cell markers (Oct4, Nanog, BMI-1, and CD44; p