The mechanism of "alteration to a cancer stem cell" in ovarian cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 26640076
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kyoto University
• Principal Investigator: Koshiyama Masafumi 京都大学, 医学(系)研究科(研究院), 講師 (50724390)
• Co-Investigator(Kenkyū-buntansha): MATSUMURA NORIOMI 京都大学, 医学研究科, 準教授 (20452336) ; BABA TSUKASA 京都大学, 医学研究科, 講師 (60508240) ; KONISHI IKUO 京都大学, 医学研究科, 教授 (90192062)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 癌幹細胞 / 化学療法耐性 / ヘッジホッグ経路 / 治療抵抗性獲得 / 卵巣癌

Outline of Final Research Achievements

Ovarian cancer frequently acquires malignant phenotypes, such as chemo-resistance and tumorgenicity. We hypothesized that suppression of a gene’s expression might cause such an acquisition. We performed a functional genomics screen using a shRNA library targeting almost all genes. As a result, we found that suppression of only a single gene’s expression caused the acquisition of malignant phenotypes of ovarian cancer. In addition, we identified at least 6 such kinds of genes. Furthermore, suppression of those 6 genes enhanced malignant phenotypes of ovarian cancer via activation of the Hedgehog pathway. When we inhibited its pathway by a specific inhibitor, cyclopamine, it markedly decreased the malignant phenotypes which had been enhanced by suppression of each of 6 genes. Our findings should be helpful for developing the new treatment for refractory ovarian cancer.

Free Research Field

癌治療