Journal
CANCER CELL
Volume 33, Issue 3, Pages 355-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2018.02.004
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Funding
- JSPS KAKENHI [24501326, 16K14621, 17K19620, 26430130, 17K07231, 16K07187, 15K14387, 16K10486]
- Takeda Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Kato Memorial Bioscience Foundation
- Uehara Memorial Foundation
- Sagawa Foundation for Promotion of Cancer Research
- Grants-in-Aid for Scientific Research [15K14387, 17K07231, 15K21098, 17K16876, 16K19745, 17K19620, 26430130, 17K19606, 17H06011, 16K07187, 16H04730, 16K14621, 16K10486, 17H05534, 16K10774, 25111006, 16K09597, 24501326, 17K07187] Funding Source: KAKEN
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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 KRAS(G12D)-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.
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