Elucidation of novel high grade transformation mechanism in oral cancer via DNA damage driven "Cancer cannibalism"

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19630
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: The University of Tokushima
• Principal Investigator: TSUNEMATSU Takaaki 徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (70726752)
• Co-Investigator(Kenkyū-buntansha): 森岡 翔 岐阜大学, 高等研究院, 客員教授 (60870029)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: がんの共食い / DNA損傷

Outline of Final Research Achievements

It is well known that dead cells are removed by professional phagocytes such as Macrophage and Dendritic cells. Whereas the engulfment of dead cancer cells by cancer cells, which can be non-professional phagocytes, is frequently observed in high grade tumors. This phenomenon is classified as a type of “Cancer cell cannibalism”. However, their biological significance and molecular mechanism largely haven’t been understood. Therefore, we established the quantitative in vitro experiment for evaluation of dead cells engulfment and explored for its regulators. Interestingly, we identified that DNA damage promoted dead cells engulfment. In addition, we also found that ATM-Chk1 pathway was important for this phenotype. Overall, our results suggested that the novel molecular mechanism of “Cancer cell cannibalism” .

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

近年、口腔がんを含めた頭頸部扁平上皮癌の全ゲノム解析がなされたものの、分子標的治療の進む他臓器のがんと異なりドライバー変異がないことが明らかとなっており、がんの免疫回避機構を標的とした免疫チェックポイント阻害薬のようにドライバー変異とは異なる観点からのがん治療法の開発が今後益々必要となってくると考えられる。つまり、新しい観点からがんの生物学を切り拓く可能性を有する“がんの共食い”は高悪性度腫瘍の治療ターゲットとして新たなブレイクスルーを生み出すポテンシャルを有していると考えられる。本研究成果で得られた“がんの共食い”の分子機構の一端を基に新しい観点からのがんの理解が進むと考えられる。