CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies.

Animals Antineoplastic Agents / pharmacology Breast Neoplasms / drug therapy CD36 Antigens / genetics Cell Line, Tumor Drug Resistance, Neoplasm Fatty Acids / metabolism Female Humans Lapatinib / pharmacology Mice Mice, Inbred NOD Protein Kinase Inhibitors / pharmacology Receptor, ErbB-2 / antagonists & inhibitors
AKT ERK FASN HER2 MAPK drug resistance lipid metabolism tyrosine kinase

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
10 12 2019
Historique:
received: 17 04 2019
revised: 22 08 2019
accepted: 04 11 2019
entrez: 12 12 2019
pubmed: 12 12 2019
medline: 24 9 2020
Statut: ppublish

Résumé

Although it is established that fatty acid (FA) synthesis supports anabolic growth in cancer, the role of exogenous FA uptake remains elusive. Here we show that, during acquisition of resistance to HER2 inhibition, metabolic rewiring of breast cancer cells favors reliance on exogenous FA uptake over de novo FA synthesis. Through cDNA microarray analysis, we identify the FA transporter CD36 as a critical gene upregulated in cells with acquired resistance to the HER2 inhibitor lapatinib. Accordingly, resistant cells exhibit increased exogenous FA uptake and metabolic plasticity. Genetic or pharmacological inhibition of CD36 suppresses the growth of lapatinib-resistant but not lapatinib-sensitive cells in vitro and in vivo. Deletion of Cd36 in mammary tissues of MMTV-neu mice significantly attenuates tumorigenesis. In breast cancer patients, CD36 expression increases following anti-HER2 therapy, which correlates with a poor prognosis. Our results define CD36-mediated metabolic rewiring as an essential survival mechanism in HER2-positive breast cancer.

Identifiants

DOI: 10.1016/j.celrep.2019.11.008 PMID: 31825825 PMC: PMC6938262
pubmed: 31825825
pii: S2211-1247(19)31479-2
doi: 10.1016/j.celrep.2019.11.008
pmc: PMC6938262
mid: NIHMS1546464
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
CD36 Antigens 0
Fatty Acids 0
Protein Kinase Inhibitors 0
Lapatinib 0VUA21238F
Receptor, ErbB-2 EC 2.7.10.1

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

3405-3420.e5

Subventions

Organisme : NCI NIH HHS
ID : P30 CA023108
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA140948
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA126618
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001088
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103534
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA208384
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA227996
Pays : United States

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

William W Feng (WW)

Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Department of Biological Sciences, Kent State University, Kent, OH 44242, USA.

Owen Wilkins (O)

Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

Scott Bang (S)

Department of Biological Sciences, Kent State University, Kent, OH 44242, USA.

Matthew Ung (M)

Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

Jiaqi Li (J)

Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

Jennifer An (J)

Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.

Carmen Del Genio (C)

Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.

Kaleigh Canfield (K)

Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

James DiRenzo (J)

Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

Wendy Wells (W)

Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA; Norris Cotton Cancer Center, Lebanon, NH 03756, USA.

Arti Gaur (A)

Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.

R Brooks Robey (RB)

Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Department of Medical Education, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; White River Junction Veterans Affairs Medical Center, White River Junction, VT 05009, USA.

Jessie Yanxiang Guo (JY)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.

Ryan L Powles (RL)

Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 05620, USA.

Christos Sotiriou (C)

Breast Cancer Translational Research Laboratory J.-C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

Lajos Pusztai (L)

Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 05620, USA.

Maria Febbraio (M)

Department of Dentistry, University of Alberta, Edmonton, AB, Canada.

Chao Cheng (C)

Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Norris Cotton Cancer Center, Lebanon, NH 03756, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

William B Kinlaw (WB)

Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Norris Cotton Cancer Center, Lebanon, NH 03756, USA.

Manabu Kurokawa (M)

Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Department of Biological Sciences, Kent State University, Kent, OH 44242, USA. Electronic address: mkurokaw@kent.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux lipoprotéines › Récepteurs aux lipoprotéines LDL › Récepteurs éboueurs › Récepteurs éboueurs de classe B › Antigènes CD36 › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Lipides › Acides gras › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinazolines › Lapatinib › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéines kinases › CD36-Mediated Metabolic Rewiring of Breast...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Récepteur ErbB-2 › CD36-Mediated Metabolic Rewiring of Breast...