論文 - 詳細
| RRC ID | 50634 |
|---|---|
| 著者 | 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. |
| タイトル | PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth. |
| ジャーナル | 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. |
| 巻・号 | 33(3) |
| ページ | 355-367.e7 |
| 公開日 | 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 |
| 引用数 | 37 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 22 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | AxCANCre (RDB01748). |
| ヒト・動物細胞 | 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) |