Addiction to Golgi-resident PI4P Synthesis in Chromosome 1q21.3-amplified Lung Adenocarcinoma Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2021 Jun 22

PMID 34155143

Citations 11

Authors

Lei Shi

Xiaochao Tan

Xin Liu

Jiang Yu

Neus Bota-Rabassedas

Yichi Niu

Jiayi Luo

Yuanxin Xi

Chenghang Zong

Chad J Creighton

Jeffrey S Glenn

Jing Wang

Jonathan M Kurie

Affiliations

Soon will be listed here.

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.

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