Explore new therapies targeting endoplasmic reticulumn stress response for Hepatocellular Carcinoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19346
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Hiroshima University
• Principal Investigator: Zhang Yizhou 広島大学, 医歯薬保健学研究科(医), 研究員 (70711117)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 肝細胞癌 / 小胞体ストレス / BBF2H7 / 分子標的治療

Outline of Final Research Achievements

Using genome-wide transcriptome profiles and in vitro validation, we elucidated the mechanism of how ER stress transducer CREB3L2/BBF2H7 promotes hepatocarcinogenesis. BBF2H7 is over-activated in hepatocellular carcinoma (HCC), and is associated with an aggressive HCC subtype correlating with poor clinical outcome. At the molecular level, we found a partial fragment of BBF2H7 to be competitively bound to a subunit of AP-1, thus blocking AP-1 transcriptional activity and indirectly suppressing the stability of p53. In rescue experiments, we demonstrated that this fragment is indispensable to the proliferation of HCC, suggesting a potential target for the treatment of this common cancer.

Free Research Field

医歯薬学