Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34155143.
- Also identified by DOI 10.1073/pnas.2023537118 and PMC identifier 8237628.
- Licence recorded as CC BY-NC-ND.
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Abstract
A chromosome 1q21.3 region that is frequently amplified in diverse cancer types encodes phosphatidylinositol (PI)-4 kinase IIIβ (PI4KIIIβ), a key regulator of secretory vesicle biogenesis and trafficking. Chromosome 1q21.3-amplified lung adenocarcinoma (1q-LUAD) cells rely on PI4KIIIβ 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 PI4KIIIβ 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.
Medical subject headings
- Adenocarcinoma of Lung
- Chromosomes, Human, Pair 1
- Gene Amplification
- Golgi Apparatus
- Phosphatidylinositol Phosphates