Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells

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

doi:10.1073/pnas.2023537118

Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells

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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Article number	e2023537118
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Issue number	25
DOIs	https://doi.org/10.1073/pnas.2023537118
State	Published - Jun 22 2021

Keywords

Cancer
Golgi
Lipids
Oncogene addiction

ASJC Scopus subject areas

General

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Flow Cytometry and Cellular Imaging Facility
Research Animal Support Facility
Bioinformatics Shared Resource

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10.1073/pnas.2023537118

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Shi, L., Tan, X., Liu, X., Yu, J., Bota-Rabassedas, N., Niu, Y., Luo, J., Xi, Y., Zong, C., Creighton, C. J., Glenn, J. S., Wang, J., & Kurie, J. M. (2021). Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells. Proceedings of the National Academy of Sciences of the United States of America, 118(25), Article e2023537118. https://doi.org/10.1073/pnas.2023537118

Shi, L, Tan, X, Liu, X, Yu, J, Bota-Rabassedas, N, Niu, Y, Luo, J, Xi, Y, Zong, C, Creighton, CJ, Glenn, JS, Wang, J & Kurie, JM 2021, 'Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 25, e2023537118. https://doi.org/10.1073/pnas.2023537118

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title = "Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells",

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.",

keywords = "Cancer, Golgi, Lipids, Oncogene addiction",

author = "Lei Shi and Xiaochao Tan and Xin Liu and Jiang Yu and Neus Bota-Rabassedas and Yichi Niu and Jiayi Luo and Yuanxin Xi and Chenghang Zong and Creighton, {Chad J.} and Glenn, {Jeffrey S.} and Jing Wang and Kurie, {Jonathan M.}",

note = "Funding Information: ACKNOWLEDGMENTS. This work was supported by the NIH through Grants R01CA181184 (to J.M.K.), R01CA2111125 (to J.M.K.), R01AI099245 (to J.S.G.), CA125123 (to C.J.C.), and U19AI109662 (to J.S.G.); NIH Lung Cancer SPORE Grant P50CA70907 (to J.M.K.); Lung Cancer Research Foundation FP#00005299 (to X.T.); and NIH Core Grant P30CA016672 for Flow Cytometry Facility, Sequencing and Microarray Facility. J.M.K. holds the Elza A. and Ina S. Freeman Endowed Professorship in Lung Cancer. The work was also supported by the generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shots Program. Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",

year = "2021",

month = jun,

day = "22",

doi = "10.1073/pnas.2023537118",

language = "English (US)",

volume = "118",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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T1 - Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells

AU - Shi, Lei

AU - Tan, Xiaochao

AU - Liu, Xin

AU - Yu, Jiang

AU - Bota-Rabassedas, Neus

AU - Niu, Yichi

AU - Luo, Jiayi

AU - Xi, Yuanxin

AU - Zong, Chenghang

AU - Creighton, Chad J.

AU - Glenn, Jeffrey S.

AU - Wang, Jing

AU - Kurie, Jonathan M.

N1 - Funding Information: ACKNOWLEDGMENTS. This work was supported by the NIH through Grants R01CA181184 (to J.M.K.), R01CA2111125 (to J.M.K.), R01AI099245 (to J.S.G.), CA125123 (to C.J.C.), and U19AI109662 (to J.S.G.); NIH Lung Cancer SPORE Grant P50CA70907 (to J.M.K.); Lung Cancer Research Foundation FP#00005299 (to X.T.); and NIH Core Grant P30CA016672 for Flow Cytometry Facility, Sequencing and Microarray Facility. J.M.K. holds the Elza A. and Ina S. Freeman Endowed Professorship in Lung Cancer. The work was also supported by the generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shots Program. Publisher Copyright: © 2021 National Academy of Sciences. All rights reserved.

PY - 2021/6/22

Y1 - 2021/6/22

N2 - 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.

AB - 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.

KW - Cancer

KW - Golgi

KW - Lipids

KW - Oncogene addiction

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U2 - 10.1073/pnas.2023537118

DO - 10.1073/pnas.2023537118

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SN - 0027-8424

VL - 118

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 25

M1 - e2023537118

ER -

Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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