Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells.
Proc Natl Acad Sci U S A
; 118(25)2021 06 22.
Article
en En
| MEDLINE
| ID: mdl-34155143
ABSTRACT
A chromosome 1q21.3 region that is frequently amplified in diverse cancer types encodes phosphatidylinositol (PI)-4 kinase IIIß (PI4KIIIß), a key regulator of secretory vesicle biogenesis and trafficking. Chromosome 1q21.3-amplified lung adenocarcinoma (1q-LUAD) cells rely on PI4KIIIß for Golgi-resident PI-4-phosphate (PI4P) synthesis, prosurvival effector protein secretion, and cell viability. Here, we show that 1q-LUAD cells subjected to prolonged PI4KIIIß antagonist treatment acquire tolerance by activating an miR-218-5p-dependent competing endogenous RNA network that up-regulates PI4KIIα, which provides an alternative source of Golgi-resident PI4P that maintains prosurvival effector protein secretion and cell viability. These findings demonstrate an addiction to Golgi-resident PI4P synthesis in a genetically defined subset of cancers.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 1
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Amplificación de Genes
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Fosfatos de Fosfatidilinositol
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Adenocarcinoma del Pulmón
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Aparato de Golgi
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2021
Tipo del documento:
Article