PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth.
Cancer Cell
; 33(3): 355-367.e7, 2018 03 12.
Article
en En
| MEDLINE
| ID: mdl-29533781
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Hormonas Tiroideas
/
Proteínas Portadoras
/
Regulación Neoplásica de la Expresión Génica
/
Transformación Celular Neoplásica
/
Proliferación Celular
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón