Clarification of microenvironment-stress induced metastasis and its targeting approach in ovarian cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390380
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: KAJIYAMA HIROAKI 名古屋大学, 医学(系)研究科(研究院), 准教授 (00345886)
• Co-Investigator(Kenkyū-buntansha): SHIBATA Kiyosumi 名古屋大学, 大学医学系研究科, 准教授 (90335026)
• Co-Investigator(Renkei-kenkyūsha): SENGA Takeshi 名古屋大学, 大学医学系研究科, 准教授 (80419431)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 卵巣癌 / 腹膜播種 / 上皮間葉転換 / 薬剤耐性 / 腹膜中皮細胞 / 転写因子

Outline of Final Research Achievements

This study aimed to generate new therapeutic approach targeting EMT-induced transcriptional factors specific for ovarian cancer (OC). We show that two homeoproteins, HOXB13 and ALX4, are associated with EMT and invasion of OC cells. HOXB13 and ALX4 formed a complex in cells and exogenous expression of either protein promoted EMT and invasion. Knockdown of HOXB13 or ALX4 suppressed SLUG expression and exogenous expression of either protein promoted SLUG expression. Finally we showed that SLUG expression was essential for the HOXB13- or ALX4-mediated EMT and invasion. Our results show that HOXB13/SLUG and ALX4/SLUG axes are novel pathways that promote EMT and invasion of OC cells. Furthermore, in the current study, we showed the role of ZEB1, a member of zinc-finger E-box binding homeobox (ZFH) family, in metastasis and chronic paclitaxel resistance in OC.

Free Research Field

婦人科腫瘍学