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The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

Author

Listed:
  • Duygu Sag

    (La Jolla Institute for Allergy and Immunology)

  • Caglar Cekic

    (Bilkent University)

  • Runpei Wu

    (La Jolla Institute for Allergy and Immunology)

  • Joel Linden

    (La Jolla Institute for Allergy and Immunology)

  • Catherine C. Hedrick

    (La Jolla Institute for Allergy and Immunology)

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.

Suggested Citation

  • Duygu Sag & Caglar Cekic & Runpei Wu & Joel Linden & Catherine C. Hedrick, 2015. "The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7354
    DOI: 10.1038/ncomms7354
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    Cited by:

    1. Lijuan Zhang & Kai Zhang & Jieyou Zhang & Jinrong Zhu & Qing Xi & Huafeng Wang & Zimu Zhang & Yingnan Cheng & Guangze Yang & Hongkun Liu & Xiangdong Guo & Dongmei Zhou & Zhenyi Xue & Yan Li & Qi Zhang, 2021. "Loss of fragile site-associated tumor suppressor promotes antitumor immunity via macrophage polarization," Nature Communications, Nature, vol. 12(1), pages 1-17, December.

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