RRC ID 50634
Author Morita M, Sato T, Nomura M, Sakamoto Y, Inoue Y, Tanaka R, Ito S, Kurosawa K, Yamaguchi K, Sugiura Y, Takizaki H, Yamashita Y, Katakura R, Sato I, Kawai M, Okada Y, Watanabe H, Kondoh G, Matsumoto S, Kishimoto A, Obata M, Matsumoto M, Fukuhara T, Motohashi H, Suematsu M, Komatsu M, Nakayama KI, Watanabe T, Soga T, Shima H, Maemondo M, Tanuma N.
Title PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth.
Journal Cancer Cell
Abstract Expression of PKM2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, PKM2 function in tumorigenesis remains controversial. Here, we show that, when expressed rather than PKM2, the PKM isoform PKM1 exhibits a tumor-promoting function in KRASG12D-induced or carcinogen-initiated mouse models or in some human cancers. Analysis of Pkm mutant mouse lines expressing specific PKM isoforms established that PKM1 boosts tumor growth cell intrinsically. PKM1 activated glucose catabolism and stimulated autophagy/mitophagy, favoring malignancy. Importantly, we observed that pulmonary neuroendocrine tumors (NETs), including small-cell lung cancer (SCLC), express PKM1, and that PKM1 expression is required for SCLC cell proliferation. Our findings provide a rationale for targeting PKM1 therapeutically in certain cancer subtypes, including pulmonary NETs.
Volume 33(3)
Pages 355-367.e7
Published 2018-3-12
DOI 10.1016/j.ccell.2018.02.004
PII S1535-6108(18)30057-6
PMID 29533781
MeSH Animals Carcinogenesis / genetics Carrier Proteins / genetics* Carrier Proteins / metabolism Cell Cycle / genetics Cell Line, Tumor Cell Proliferation / genetics* Cell Transformation, Neoplastic / genetics* Gene Expression Regulation, Neoplastic / genetics* Membrane Proteins / genetics* Membrane Proteins / metabolism Mice, Knockout Protein Isoforms / genetics Thyroid Hormones / genetics*
IF 26.602
Times Cited 37
DNA material AxCANCre (RDB01748).
Human and Animal Cells T3M-12(RCB2281) Lu-134-A(RCB0466) Lu-138(RCB1785) Lu-139(RCB0469) Lu-140(RCB0470) Lu-141(RCB1772) Lu-143(RCB1773) Lu-165(RCB1184) 87-5(RCB2092) A549(RCB0098) 293(RCB1637) HeLa(RCB0007)