Molecular mechanism for the onset of cervical cancer by HPV virus

2016 Fiscal Year Final Research Report

• Project/Area Number: 26640081
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kobe University (2016); Kyushu University (2014-2015)
• Principal Investigator: Suzuki Akira 神戸大学, 医学研究科, 教授 (10311565)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 子宮頸がん / Hippo経路

Outline of Final Research Achievements

To investigate function of Hippo for the onset of cervical epithelium, we generated progesterone receptor-Cre, Mob1afl/fl, Mob1b-/- mice (cDKO). All of cDKO mice showed cervical cancers 3 weeks after birth. cDKO cervical epithelial cells exhibited hyperproliferation, impaired contact inhibition, enhanced progenitor self renewal, and increased centrosomes. Examination of Hippo pathway signaling in cDKO cervical epithelial cells revealed that loss of Mob1a/b altered the activities of the downstream Hippo mediators LATS and YAP1. Similarly, YAP1 was activated in human cervical carcinomas. And expression of HPV E6 and E7 in HPV non-infected cervical epithelial cells shows activation of YAP. Taken together, our results indicate that HPV causes cervical cancers by modulating Hippo signaling pathway.

Free Research Field

腫瘍学