No abstract

Excess body weight and obesity have become significant risk factors for cancer development. During obesity, adipose tissue alters its biological function, deregulating the secretion of bioactive factors such as hormones, cytokines, and adipokines that promote an inflammatory microenvironment conducive to carcinogenesis and tumor progression. Adipokines regulate tumor processes such as apoptosis, proliferation, migration, angiogenesis, and invasion. Additionally, it has been found that they can modulate autophagy, a process implicated in tumor suppression in healthy tissue and cancer progression in established tumors. Since the tumor-promoting role of autophagy has been well described, the process has been suggested as a therapeutic target in cancer. However, the effects of targeting autophagy might depend on the tumor type and microenvironmental conditions, where circulating adipokines could influence the role of autophagy in cancer. Here, we review recent evidence related to the role of adipokines in cancer cell autophagy in an effort to understand the tumor response in the context of obesity under the assumption of an autophagy-targeting treatment.

Autophagy is an intracellular recycling process active in eukaryotic cells that involves the formation of an autophagosome which delivers cytoplasmic components to the lysosome for degradation. This process occurs at low rates under basal conditions, but it can be induced by diverse types of stress such as starvation, hypoxia, metabolic disorders or in response to hormones, including leptin. Leptin is considered a pro-tumorigenic protein whose circulating levels have been related to bad prognosis in obese breast cancer patients. It has been recently demonstrated that leptin can induce autophagy in cancer cell lines from different tissues, suggesting that autophagy could modulate the pro-tumorigenic effects associated with leptin. In this study, the role of autophagy in leptin-induced proliferation, migration, apoptosis and ERK phosphorylation in breast cancer cell lines was evaluated. Although leptin differentially induced autophagy in the breast cancer cell lines tested, autophagy inhibition reduced leptin-induced cell proliferation in MCF7 cells and decreased cell migration, ERK activation, and impaired morphological changes in both cell lines. Our data demonstrates an important role for basal autophagy or leptin-induced autophagy in leptin-induced migration and ERK phosphorylation in breast cancer cell lines, suggesting a potential use for the inhibition of autophagy in breast cancer associated with obesity.