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Cited by 205Immune cells in cancerCancer, Lipids, and MetabolismCholesterol and Lipid Metabolism

The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

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Sag, Duygu, Cekic, Caglar, Wu, Runpei, Linden, Joel, Hedrick, Catherine C.·2015·Nature Communications
DOI 10.1038/ncomms7354PMC PMC4347884
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Abstract

ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1−/− mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1−/− mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1−/− macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer. ABCG1 transporter pumps cholesterol out of the cell. Here, the authors show that ABCG1-deficient mice have reduced tumour growth due to a switch of the tumour-associated macrophages from a tumour-promoting to tumour-suppressing phenotype, and are protected from the pro-tumorigenic effects of a Western-like diet.

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  • Knockdown of ABCG1 resulted in inhibited tumor growth, but in a different study this required a physiologic challenge (western diet, age or genetic model of hypercholesterolemia).

    “Knockdown of the related transporter ABCG1 also resulted in inhibited tumor growth (75), but in a different study this required a physiologic challenge (western diet, age or genetic model of hypercholesterolemia) (76).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [76]

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Authors
Sag, D., Cekic, C., Wu, R., Linden, J., & Hedrick, C. C.
Affiliations
  • Bilkent University (TR)
  • La Jolla Institute for Immunology (US)
Corresponding author
Hedrick, Catherine C.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2015-02-27
Volume
6
Issue
1
Pages
6354-6354
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms7354
PMC
PMC4347884
OpenAlex
W2011918640
Cited by
205
References
5
Citations by year
2026: 8 · 2025: 26 · 2024: 27 · 2023: 39 · 2022: 23 · 2021: 22 · 2020: 16 · 2019: 11 · 2018: 12 · 2017: 8 · 2016: 9 · 2015: 4
FWCI
5.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Bilkent University Institutional Repository (Bilkent University) (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (P01HL55798, P01HL055798, R01HL097368, P01HL073361)
  • National Center for Research Resources (S10RR027366)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
ABCG1, cholesterol efflux, cholesterol homeostasis, tumour immunity, tumour-associated macrophages, macrophage polarization, NF-κB activation, macrophage cytotoxicity, bladder cancer, melanoma, tumor growth inhibition
MeSH terms
ATP Binding Cassette Transporter, Subfamily G, Member 1, Animals, Urinary Bladder Neoplasms, Carcinoma, Cholesterol, Flow Cytometry, Fluorescence, Homeostasis, Lipoproteins, Macrophages, Melanoma, Mice, Inbred C57BL, Mice, Knockout, ATP-Binding Cassette Transporters, Cell Line, Tumor, Mice, Real-Time Polymerase Chain Reaction

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