Clarification of the PKM2 function and the regulation mechanism among its related factors in the oral malignant tumor

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07033
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Fukuoka Dental College
• Principal Investigator: Hashimoto Shuichi 福岡歯科大学, 口腔歯学部, 教授 (00243931)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: PKM2 / EMT / TGIF2 / OSCC / Warburg effect

Outline of Final Research Achievements

PKM2 acts as a glycolytic enzyme on the energy generation in cancers. PKM2 expression was seen in the cytoplasm in human oral squamous cell carcinoma (OSCC) and the nuclei in the EMT-induced cancer cells. TGIF2 was expressed in the nuclei in dysplastic cells but repressed in cancer cells. When EMT was induced in HSC-4, a human derived OSCC, PKM2 expression was translocated from the cytoplasm into the nucleus. Intra-nuclear expression of TGIF2 was inhibited but the mRNA expression was maintained. It was revealed that TGIF2 protein was post-translationally repressed. By the knockdown analysis, PKM2 promoted the progression of HSC-4 migration and invasion. From these findings, we clarified a non-metabolic function of PKM2 that nuclear PKM2 promoted the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing
TGIF2.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

解糖酵素の一つであるPKM2はWarburg効果として知られる癌進展におけるエネルギー産生をもたらす代謝機能として働くことが知られている。本研究において、我々は、PKM2がヒト口腔扁平上皮癌（OSCC）において癌浸潤に極めて重要な上皮間葉転換（EMT）およびTGIF2の翻訳後分解を介して癌細胞の進展を増強する非代謝的機能としても働くという極めて重要な役割を持つことを示した。この新たな知見により、口腔癌の進展における新たなメカニズムの一つが明らかとなり、新しい口腔癌の治療法の開発につながる可能性が示されたことに学術的および社会的意義があると考えられる。