The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

Date

2015

Authors

Sag, D.
Cekic, C.
Wu, R.
Linden J.
Hedrick, C.C.

Editor(s)

Advisor

Supervisor

Co-Advisor

Co-Supervisor

Instructor

Source Title

Nature Communications

Print ISSN

20411723

Electronic ISSN

Publisher

Nature Publishing Group

Volume

6

Issue

Pages

Language

English

Journal Title

Journal ISSN

Volume Title

Usage Stats
1
views
7
downloads

Series

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. © 2015 Macmillan Publishers Limited. All rights reserved.

Course

Other identifiers

Book Title

Degree Discipline

Degree Level

Degree Name

Citation

Published Version (Please cite this version)