Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells

Jeong-Ran Park, Ran-Ju Kim, Yoo-Kyung Lee, Soo-Rim Kim, Kyung-Jin Roh, Seung Hyun Oh, Gu Kong, Kyung-Sun Kang, Jeong-Seok Nam
Journal of Hepatology 2011, 54 (1): 122-31

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence, and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC.

METHODS: We analyzed the functional implications of dysadherin on cancer stemness by modification of the dysadherin gene in HCC cell lines.

RESULTS: The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSCs, including anti-apoptosis, their sphere-forming ability, side population phenotype, and tumor initiation ability in vivo. Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties.

CONCLUSIONS: These results show that dysadherin give rise to properties of CSC in HCC. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies.

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