Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration

TLDR

Obesity is linked to higher breast cancer recurrence and poorer survival, yet the contribution of breast tissue adipocytes to tumor metabolism remains unclear. Adipocytes release free fatty acids that are taken up by breast cancer cells, upregulating CPT1A and electron‑transport‑chain proteins to fuel proliferation and migration. Co‑culture experiments show that adipocyte lipolysis supplies fatty acids that boost breast cancer cell proliferation and migration, especially from obese adipocytes, and that silencing HSL/ATGL reduces these effects.

Abstract

Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from "obese" adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses. These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression.