がん研セミナー（９月８日）のお知らせ

演題：Deciphering the Anti-Tumor Effect of Tumorigenic Molecules in Liver Cancer

演者：Gen-Sheng Feng 博士（Professor, Department of Pathology, University of California San Diego, La Jolla, CA, USA.）

日時：2014年 9月8日（月）16:00-17:00

場所：吉田講堂

連絡先：原　英二（内線5351）

抄録：　

Many of the classical oncogenic pathways have been shown to play key roles in driving HCC development, and therefore have naturally become therapeutic targets. Unfortunately, pharmaceuticals that are designed to block the primary tumorigenic signals have achieved very little curative effect.

Consistently, we and others have uncovered anti-oncogenic effects for a number of pro-oncogenic molecules, including c-Met, NF-kB, b-catenin, Stat3, Jnk1/2 and Shp2, in mouse HCC models. We believe that elucidating the “paradoxical” effects of these molecules will provide fundamental insights into the mechanisms of drug resistance and will also offer new therapeutic strategies for liver cancer. More recently, we have found that Shp2 couples the intrahepatic and enterohepatic signals for repression of bile acid (BA) synthesis. Ablating Shp2 in hepatocytes suppressed signal relay from FGFR4 and also attenuated BA activation of nuclear receptor FXR signaling, resulting in elevation of systemic BA levels and chronic hepatobiliary disorders in mice. Consistently, several groups reported that excess BAs are hepatocarcinogenic.

References:

1. Bard-Chapeau et al. Ptpn11/Shp2 acts as a tumor suppressor in

hepatocellular carcinogenesis. Cancer Cell 19: 629-639

2. Feng GS. 2012. Conflicting roles of molecules in hepatocarcinogenesis: paradigm or paradox. Cancer Cell 21: 150-154

3. Li et al., Cytoplasmic tyrosine phosphatase Shp2 coordinates hepatic regulation of bile acid and FGF15/19 signaling to repress bile acid synthesis. Cell Metabolism. In press, 2014.

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