Gene Responsible for Bile Duct Cancer Identified and Relevant Therapy Discovered

Release date: 2015.12.22


Research Results Life & Health

 In collaboration with Kyushu University Beppu Hospital and the National Institute of Advanced Industrial Science and Technology (Tsukuba, Ibaraki Prefecture), a research team including Assistant Professor Miki Nishio of the Kyushu University Medical Institute of Bioregulation and Professor Akira Suzuki discovered that the MOB1 signaling pathway is a key factor in intrahepatic cholangiocellular carcinoma and combined hepatocellular and cholangiocarcinoma.

 Moreover, the research team explored natural substances that target this signaling pathway and discovered that the antiparasitic drug ivermectin, which was one of the subjects of this year’s Nobel Prize in Physiology or Medicine, could become a drug for treating intrahepatic cholangiocellular carcinoma. It is hoped that this discovery will improve the prognosis for patients with intrahepatic cholangiocellular carcinoma or combined hepatocellular and cholangiocarcinoma, which currently have the worst prognoses of all liver cancers. This study was supported by the Ministry of Education, Culture, Sports, Science and Technology and, from FY2015, the Program for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) run by the Japan Agency for Medical Research and Development.
 The outcomes of this study were published in the online edition of the Proceedings of the National Academy of Sciences of the United States of America at 15:00 (Eastern Standard Time) on Monday, December 21, 2015.

Liver tumors observed in LMob1DKO mice.

Mob1a/1b-deficient liver phenotypes are dependent on Yap1, Taz, and Tgfbs but not on Ctgf. Analyses of livers from Mob1a/1b triple mutant (TKO) strains.

Representative macroscopic analyses and H&E staining and YAP1 immunostaining of livers from DMSO-treated control mice and LDKO mice treated with DMSO or ivermectin.

Journal Reference

Dysregulated YAP1/TAZ and TGF-beta signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice, ,Nishio M, Sugimachi K, et al., Proceedings of the National Academy of Sciences of the United States of America 113(1), E71-80, 2016,

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