Functional analysis of PTPRK-CD133 regulatory axis in colon cancer progression.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462033
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Souda Hiroaki 千葉県がんセンター(研究所), 消化器外科, 主任医長 (90261940)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 大腸癌 / 癌性幹細胞 / CD133 / PTPRK

Outline of Final Research Achievements

As a higher expression of receptor-type protein tyrosine phosphatase (PTPRK) is considered to be a good prognostic factor for the CD133-expressing colon cancer patients, we sought to investigate the functional significance of the PTPRK-CD133 regulatory axis in the malignant properties of colon cancer cells. Based on our present observations, forced expression of CD133 enhanced a xenograft tumor growth of colon cancer cells and knockdown of PTPRK further promoted the CD133-induced tumor formation in vivo. PTPRK is directly implicated in the dephosphorylation of CD133 in human colon cancer cells. Additionally, PTPRK-depletion dramatically stimulated an anti-apoptotic function of Bad through the activation of the oncogenic CD133-AKT pathway, and thereby significantly reduced an anti-tumor drug-induced cell death. Together, our present observations strongly suggest that the PTPRK-CD133 regulatory axis plays a pivotal role in the regulation of colon cancer progression and drug resistance.

Free Research Field

消化器外科