BAD, a proapoptotic member of the BCL2 family, is a potential therapeutic target in hepatocellular carcinoma

Molecular Cancer Research : MCR
Antoine GalmicheDenis Chatelain

Abstract

Proteins of the BCL2 family are key regulators of apoptosis. Their expression levels are frequently altered in cancers, enabling tumor cells to survive. To gain insight into the pathogenesis of hepatocellular carcinoma (HCC), we performed a comprehensive survey of the expression of the members of the BCL2 family in samples obtained from surgically resected HCCs. Here, we report the occurrence of a new molecular anomaly, consisting of a strong reduction in the expression of the proapoptotic protein BAD in HCC compared with surrounding nontumoral tissue. We investigate the function of BAD in a panel of HCC cell lines. Using gene overexpression and RNA interference, we show that BAD is involved in the cytotoxic effects of sorafenib, a multikinase blocker, which is currently the sole therapeutic drug effective for the treatment of HCC. Finally, we report that ABT-737, a compound that interacts with proteins of the BCL2 family and exhibits a BAD-like reactivity, sensitizes HCC cells toward sorafenib-induced apoptosis. Collectively, our findings indicate that BAD is a key regulator of apoptosis in HCC and an important determinant of HCC cell response to sorafenib.

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Citations

Dec 17, 2011·Biochemical and Biophysical Research Communications·Eric TrécherelAntoine Galmiche
Aug 18, 2012·Journal of Molecular Signaling·Vasileios A StamelosAlan Richardson
Apr 20, 2012·International Journal of Cancer. Journal International Du Cancer·Zakaria EzzoukhryAntoine Galmiche
Mar 19, 2013·International Journal of Cancer. Journal International Du Cancer·Christophe LouandreAntoine Galmiche
Jun 20, 2015·BioMed Research International·Junsheng ChengYoucheng Zhang
Oct 29, 2011·Gynecologic Oncology·Hye Sook ChonJohnathan M Lancaster
Jan 30, 2020·Frontiers in Oncology·Huapeng ZhangShuijun Zhang
May 8, 2018·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Norelia TorrealbaMar Royuela
Apr 4, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hetal BrahmbhattDavid W Andrews

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