BET bromodomain proteins control breast cancer aggressiveness promoted by adipocyte-derived exosomes
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Cells can release lipid bilayer vesicles of endosomal and plasma membrane origin, which are known as exosomes or extracellular vesicles (EVs). EVs contain diverse shuttling lipids, RNA and transmembrane proteins, and play an important role in communicating between neighboring or distant cells. Breast cancer is the most commonly diagnosed malignancy, with over 2 million new cases in 2018, and is the leading cause of cancer mortality in women all over the world. Some observational studies have suggested that breast cancer is more likely to develop among women who have type 2 diabetes; the association is clear in postmenopausal women. Moreover, women with type 2 diabetes diagnosed before, at the same time, or after breast cancer diagnosis, have decreased overall survival compared to women without diabetes. The most recent medical studies provide more clues as to why breast cancer is more common and has poorer prognosis in type 2 diabetes patients, by pointing out the role of insulin-resistant adipocytes in the etiopathology. Here, we demonstrate how insulin-resistant adipocytes engage crosstalk with breast cancer cells through EVs in the microenvironment and drive the tumor cells to be more metastatic and aggressive. These progression mechanisms and the effects of insulin-resistant adipocytes on breast cancer cells require Bromodomain and ExtraTerminal (BET) proteins – an important epigenetic pathway. Targeting this pathway may help reduce morbidity and mortality of women with breast cancer and type 2 diabetes.
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