Investigation of roles of pliripotency-related genes on cancer stem cells using CRISPR-Cas9 genome editing

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670156
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University
• Principal Investigator: Kaneda Yasufumi 大阪大学, 医学(系)研究科(研究院), 教授 (10177537)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 癌幹細胞 / 多能性維持因子 / ゲノム編集

Outline of Final Research Achievements

NANOG expression in prostate cancer is highly correlated with cancer stem cell characteristics and resistance to chemotherapy. However, it is not clear whether NANOG or its pseudogenes contribute to the malignant potential of cancer. We established NANOG- and NANOGP8-knockout DU145 prostate cancer cell lines using the CRISPR/Cas9 system. Knockouts of NANOG and NANOGP8 significantly attenuated malignant potential, including sphere formation, anchorage-independent growth, migration capability, and drug resistance, compared to parental DU145 cells. NANOG and NANOGP8 knockout did not inhibit in vitro cell proliferation, but in vivo tumorigenic potential decreased significantly. These phenotypes were recovered in NANOG- and NANOGP8-rescued cell lines. These results indicate that NANOG and NANOGP8 proteins are expressed in prostate cancer cell lines, and NANOG and NANOGP8 equally contribute to the high malignant potential of prostate cancer.

Free Research Field

病態医科学