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

被引：188

作者：

Hamabe, Atsushi ^{[1
,2
]}

Konno, Masamitsu ^{[2
]}

Tanuma, Nobuhiro ^{[3
]}

Shima, Hiroshi ^{[3
]}

Tsunekuni, Kenta ^{[1
,4
,5
]}

Kawamoto, Koichi ^{[1
,2
]}

Nishida, Naohiro ^{[2
]}

Koseki, Jun ^{[5
]}

Mimori, Koshi ^{[6
]}

Gotoh, Noriko ^{[7
]}

Yamamoto, Hirofumi ^{[1
]}

Doki, Yuichiro ^{[1
,2
,5
]}

Mori, Masaki ^{[1
,2
,5
]}

Ishii, Hideshi ^{[2
,5
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Gastrointestinal Surg, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med, Dept Frontier Sci Canc & Chemotherapy, Osaka 5650871, Japan

[3] Miyagi Canc Ctr Res Inst, Div Canc Chemotherapy, Sendai, Miyagi 9811293, Japan

[4] Taiho Pharmaceut Co Ltd, Chiyoda Ku, Tokyo 1010054, Japan

[5] Osaka Univ, Grad Sch Med, Dept Canc Profiling Discovery, Osaka 5650871, Japan

[6] Kyushu Univ, Beppu Hosp, Dept Surg, Beppu, Oita 8740838, Japan

[7] Kanazawa Univ, Canc Res Inst, Div Canc Cell Biol, Kanazawa, Ishikawa 9201192, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 43期

基金：

日本学术振兴会;

关键词：

pyruvate kinase M2; epithelial-mesenchymal transition; colorectal cancer; invasion; transforming growth factor-beta-induced factor homeobox 2; CANCER; BETA; GENE; EXPRESSION; ISOFORM; TGIF2; TALE;

D O I：

10.1073/pnas.1407717111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-beta-induced factor homeobox 2 (TGIF2), a transcriptional cofactor repressor of TGF-beta 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.

引用

页码：15526 / 15531

页数：6

共 28 条

[1]

[Anonymous], CA CANC J CLIN, DOI DOI 10.3322/CAAC.20107

[2] The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth [J].