Adipocytes Promote Breast Cancer Cell Survival and Migration through Autophagy Activation

Simple Summary Breast tumours are in direct contact with the adipose tissue of the mammary gland. Although the interactions between breast cancer cells and adipocytes that secrete tumour-promoting factors are well known, the molecular mechanisms remain under investigation. The aim of our study was to understand whether and how adipocytes regulate a cell-recycling pathway in breast cancer cells-autophagy. We show that adipocytes promote autophagy in breast cancer cells through the acidification of lysosomes, leading to cancer cell survival in nutrient-deprived conditions and to cancer cell migration. In this study, we have identified a new mechanism, which can link adipose tissue with breast cancer progression. White adipose tissue interacts closely with breast cancers through the secretion of soluble factors such as cytokines, growth factors or fatty acids. However, the molecular mechanisms of these interactions and their roles in cancer progression remain poorly understood. In this study, we investigated the role of fatty acids in the cooperation between adipocytes and breast cancer cells using a co-culture model. We report that adipocytes increase autophagy in breast cancer cells through the acidification of lysosomes, leading to cancer cell survival in nutrient-deprived conditions and to cancer cell migration. Mechanistically, the disturbance of membrane phospholipid composition with a decrease in arachidonic acid content is responsible for autophagy activation in breast cancer cells induced by adipocytes. Therefore, autophagy might be a central cellular mechanism of white adipose tissue interactions with cancer cells and thus participate in cancer progression.