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
de 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Chromosomes humains de la paire 1
/
Amplification de gène
/
Phosphates phosphatidylinositol
/
Adénocarcinome pulmonaire
/
Appareil de Golgi
Limites:
Humans
Langue:
En
Journal:
Proc Natl Acad Sci U S A
Année:
2021
Type de document:
Article