BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment

Andrieu, Guillaume P and Shafran, Jordan S and Deeney, Jude T and Bharadwaj, Kishan R and Rangarajan, Annapoorni and Denis, Gerald V (2018) BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment. In: JOURNAL OF LEUKOCYTE BIOLOGY, 104 (2). pp. 265-274.

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Abstract

Obesity and its associated pathology Type 2 diabetes are two chronic metabolic and inflammatory diseases that promote breast cancer progression, metastasis, and poor outcomes. Emerging critical opinion considers unresolved inflammation and abnormal metabolism separately from obesity; settings where they do not co-occur can inform disease mechanism. In breast cancer, the tumor microenvironment is often infiltrated with T effector and T regulatory cells programmed by metabolic signaling. The pathways by which tumor cells evade immune surveillance, immune therapies, and take advantage of antitumor immunity are poorly understood, but likely depend on metabolic inflammation in the microenvironment. Immune functions are abnormal in metabolic disease, and lessons learned from preclinical studies in lean and metabolically normal environments may not translate to patients with obesity and metabolic disease. This problem is made more urgent by the rising incidence of breast cancer among women who are not obese but who have metabolic disease and associated inflammation, a phenotype common in Asia. The somatic BET proteins, comprising BRD2, BRD3, and BRD4, are newcritical regulators of metabolism, coactivate transcription of genes that encode proinflammatory cytokines in immune cell subsets infiltrating the microenvironment, and could be important targets in breast cancer immunotherapy. These transcriptional coregulators are well known to regulate tumor cell progression, but only recently identified as critical for metabolism, metastasis, and expression of immune checkpoint molecules. We consider interrelationships among metabolism, inflammation, and breast cancer aggressiveness relevant to the emerging threat of breast cancer among women with metabolic disease, but without obesity.

Item Type:	Journal Article
Publication:	JOURNAL OF LEUKOCYTE BIOLOGY
Publisher:	WILEY
Additional Information:	Copy right for this article belong to WILEY
Keywords:	BET proteins; breast cancer; chronic inflammation; metabolic disease; Type 2 diabetes
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	05 Oct 2018 15:07
Last Modified:	05 Oct 2018 15:07
URI:	http://eprints.iisc.ac.in/id/eprint/60819

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