Characteristics of human cancers showing high-level centrosome amplification and their sensitivity to drugs targeting centrosome amplification

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08709
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Shinmura Kazuya 浜松医科大学, 医学部, 准教授 (40321880)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 中心体数的異常 / 中心体過剰複製 / WDR62 / POLQ / DNA グリコシラーゼ

Outline of Final Research Achievements

The followings were revealed in this study: (1) Overexpression of WDR62, which is localized in centrosome and cytoplasm, is associated with a poor prognosis in patients with lung adenocarcinoma (LAC) and concurrent overexpression of WDR62 and TPX2, a WDR62-interacting protein that is also overexpressed in LAC, induced centrosome amplification via AURKA activation in lung cells. 　(2) Overexpression of POLQ, one of translesion DNA synthesis polymerase, is associated with advanced pathologic stage, increased somatic mutation load, and PLK4 overexpression, the last inducing centrosome amplification, in LAC, suggesting that POLQ overexpression is involved in the pathogenesis of LAC. 　(3) Overexpression of centrosomal protein STIL in lung cancer is associated with high-level abnormality in chromosomal copy number, suggesting the induction of chromosomal numerical abnormality resulting from centrosome amplification due to STIL overexpression in lung cancer.

Free Research Field

腫瘍病理学

Academic Significance and Societal Importance of the Research Achievements

癌における中心体過剰複製を起こす要因や機構、および、中心体過剰複製と関連する癌形質に関する理解が深まった。将来的な癌治療戦略に貢献でき、国民の福祉向上につながる可能性があるものと思われる。