Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial–mesenchymal transition

Atsushi Hamabe; Masamitsu Konno; Nobuhiro TanumaHiroshi ShimaKenta TsunekuniKoichi KawamotoNaohiro NishidaJun KosekiKoshi MimoriNoriko GotohHirofumi YamamotoYuichiro DokiMasaki MoriHideshi Ishii

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Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial–mesenchymal transition

机译：Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial–mesenchymal transition

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Pyruvate kinase M2 (PKM2) is an alternatively spliced variant of the pyruvate kinase gene that is preferentially expressed during embryonic development and in cancer cells. PKM2 alters the final rate-limiting step of glycolysis, resulting in the cancer-specific Warburg effect (also referred to as aerobic glycolysis). Although previous reports suggest that PKM2 functions in nonmetabolic transcriptional regulation, its significance in cancer biology remains elusive. Here we report that stimulation of epithelial–mesenchymal transition (EMT) results in the nuclear translocation of PKM2 in colon cancer cells, which is pivotal in promoting EMT. Immunoprecipitation and LC-electrospray ionized TOF MS analyses revealed that EMT stimulation causes direct interaction of PKM2 in the nucleus with TGF-β–induced factor homeobox 2 (TGIF2), a transcriptional cofactor repressor of TGF-β signaling. The binding of PKM2 with TGIF2 recruits histone deacetylase 3 to the E-cadherin promoter sequence, with subsequent deacetylation of histone H3 and suppression of E-cadherin transcription. This previously unidentified finding of the molecular interaction of PKM2 in the nucleus sheds light on the significance of PKM2 expression in cancer cells.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第43期|15526-15531|共6页
作者
Atsushi Hamabe; Masamitsu Konno; Nobuhiro TanumaHiroshi ShimaKenta TsunekuniKoichi KawamotoNaohiro NishidaJun KosekiKoshi MimoriNoriko GotohHirofumi YamamotoYuichiro DokiMasaki MoriHideshi Ishii;
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作者单位

Division of Cancer Cell Biology, Cancer Research Institute of Kanazawa University, Kanazawa 920-1192, Japan;

Departments of Gastrointestinal Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan;

Departments of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, JapanDivision of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Sendai 981-1293, JapanDepartment of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Osaka 565-0871, JapanDepartment of Surgery, Kyushu University Beppu Hospital, Beppu 874-0838, Japan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
pyruvate kinase M2; epithelial–mesenchymal transition; colorectal cancer; invasion; transforming growth factor-β–induced factor homeobox 2;

Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial–mesenchymal transition

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