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The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity
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Journal Article
The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity
2015
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/2
/ 13/21
/ 13/31
/ 38
/ 38/77
/ 59
/ 59/5
/ Animals
/ ATP Binding Cassette Transporter, Sub-Family G, Member 1
/ ATP-Binding Cassette Transporters - genetics
/ ATP-Binding Cassette Transporters - metabolism
/ Bladder
/ Diet
/ Humanities and Social Sciences
/ Melanoma
/ Mice
/ Plasma
/ Real-Time Polymerase Chain Reaction
/ Science
/ Tumors
