| Literature DB >> 29533781 |
Mami Morita1, Taku Sato2, Miyuki Nomura3, Yoshimi Sakamoto3, Yui Inoue3, Ryota Tanaka2, Shigemi Ito3, Koreyuki Kurosawa3, Kazunori Yamaguchi4, Yuki Sugiura5, Hiroshi Takizaki6, Yoji Yamashita3, Ryuichi Katakura3, Ikuro Sato7, Masaaki Kawai3, Yoshinori Okada8, Hitomi Watanabe9, Gen Kondoh9, Shoko Matsumoto10, Ayako Kishimoto10, Miki Obata11, Masaki Matsumoto12, Tatsuro Fukuhara13, Hozumi Motohashi14, Makoto Suematsu5, Masaaki Komatsu11, Keiichi I Nakayama12, Toshio Watanabe10, Tomoyoshi Soga15, Hiroshi Shima16, Makoto Maemondo17, Nobuhiro Tanuma18.
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.Entities:
Keywords: PKM; PKM1; PKM2; autophagy; glucose metabolism; lung neuroendocrine tumor; mitophagy; small-cell lung cancer
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Year: 2018 PMID： 29533781 DOI： 10.1016/j.ccell.2018.02.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743