Development of cancer stem cell-targeted therapy by study of tumor sphere formation mechanism using comprehensive and genetic approach

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390269
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Research Institute for Clinical Oncology, Saitama Cancer Center (2014); Chiba Cancer Center (Research Institute) (2012-2013)
• Principal Investigator: KAMIJO Takehiko 埼玉県立がんセンター(臨床腫瘍研究所), その他部局等, その他 (90262708)
• Co-Investigator(Kenkyū-buntansha): 田尻 達郎 京都府立医科大学, 大学院, 教授 (80304806) ; 吉田 英生 千葉大学医学系研究科, 研究院, 教授 (60210712) ; 竹信 尚典 千葉県がんセンター, 研究所, 研究員 (60392247) ; 春田 雅之 埼玉県立がんセンター, 臨床腫瘍研究所, 研究員 (80392190)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 癌幹細胞 / 腫瘍スフェア / 神経芽腫

Outline of Final Research Achievements

We performed screening of molecules which specifically expressed in neuroblastoma sphere and its high expression related to poor prognosis of neuroblastoma patients. Finally, we identified two interesting candidates by the wet/dry experiments; the candidate molecules were co-receptor molecule CXX1 and transcription factor HXX1. Knockdown of co-receptor molecule CXX1 in sphere-forming neuroblastoma cells successfully inhibited sphere formation.
Further, using yeast two-hybrid screening, we identified receptor-type protein tyrosine phosphatase K (PTPRK) as a binding partner of CD133, a cancer stemness-related molecule. Silencing of PTPRK elevated the tyrosine phosphorylation of CD133, while forced expression of PTPRK reduced its phosphorylation level markedly and abrogated CD133-mediated AKT phosphorylation. The tyrosine phosphorylation of CD133, which is dephosphorylated by PTPRK, regulates AKT signaling and plays a critical role in tumorigenesis (ONCOGENE, 2015).

Free Research Field

小児科学、腫瘍細胞生物学