biostudies-literatureJafari NNIDDK NIH HHSNCI NIH HHSeabj2807https://www.ebi.ac.uk/biostudies/studies/S-EPMC8765301biostudies-literatureUnknown14(710)Obesity and metabolic diseases, such as insulin resistance and type 2 diabetes (T2D), are associated with metastatic breast cancer in postmenopausal women. Here, we investigated the critical cellular and molecular factors behind this link. We found that primary human adipocytes shed extracellular vesicles, specifically exosomes, that induced the expression of genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem–like cell (CSC) traits in cocultured breast cancer cell lines. Transcription of these genes was further increased in cells exposed to exosomes shed from T2D patient–derived adipocytes or insulin-resistant adipocytes and required the epigenetic reader proteins BRD2 and BRD4 in recipient cells. The thrombospondin family protein TSP5, which is associated witScience signalingAdipocyte-derived exosomes may promote breast cancer progression in type 2 diabetes.PMC8765301R01 CA222170P30 DK046200U01 CA182898R01 DK117161U01 CA243004Qiu YEnnis CSPompa IRMazzeo CSMeshulam TShafran JSRabhi NJafari NKolla MCasey ANFarmer SRDenis GVfalseAdipocyte-derived exosomes may promote breast cancer progression in type 2 diabetes.Obesity and metabolic diseases, such as insulin resistance and type 2 diabetes (T2D), are associated with metastatic breast cancer in postmenopausal women. Here, we investigated the critical cellular and molecular factors behind this link. We found that primary human adipocytes shed extracellular vesicles, specifically exosomes, that induced the expression of genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem–like cell (CSC) traits in cocultured breast cancer cell lines. Transcription of these genes was further increased in cells exposed to exosomes shed from T2D patient–derived adipocytes or insulin-resistant adipocytes and required the epigenetic reader proteins BRD2 and BRD4 in recipient cells. The thrombospondin family protein TSP5, which is associated wit2021-01-01T00:00:00Z2021 Nov2026-05-31T20:59:51.994Z2025-04-04T21:43:22.785ZS-EPMC87653013481335910.1126/scisignal.abj2807