Unraveling the Role of Hepatic PGC1a in Breast Cancer Invasion: A New Target for Therapeutic Intervention?

Breast cancer (BC) is the most common cancer among women worldwide and the main cause of cancer deaths in women. Metabolic components are key risk factors for the development of non-alcoholic fatty liver disease (NAFLD), which may promote BC. Studies have reported that increasing PGC1a levels increases mitochondrial biogenesis, thereby increasing cell proliferation and metastasis. Moreover, the PGC1a/ERRa axis is a crucial regulator of cellular metabolism in various tissues, including BC. However, it remains unclear whether NAFLD is closely associated with the risk of BC. Therefore, the present study aimed to determine whether hepatic PGC1a promotes BC cell invasion via ERRa. Various assays, including ELISA, western blotting, and immunoprecipitation, have been employed to explore these mechanisms. According to the KM plot and TCGA data, elevated PGC1a expression was highly associated with a shorter overall survival time in patients with BC. High concentrations of palmitic acid (PA) promoted PGC1a expression, lipogenesis, and inflammatory processes in hepatocytes. Conditioned medium obtained from PA-treated hepatocytes significantly increased BC cell proliferation. Similarly, recombinant PGC1a in E0771 and MCF7 cells promoted cell proliferation, migration, and invasion in vitro. However, silencing PGC1a in both BC cell lines resulted in a decrease in this trend. As determined by immunoprecipitation assay, PCG1a interacted with ERRa, thereby facilitating the proliferation of BC cells. This outcome recognizes the importance of further investigations in exploring the full potential of hepatic PGC1a as a prognostic marker for BC development.

Automated summary

The present study aimed to determine whether hepatic PGC1a promotes BC cell invasion via ERRa. Elevated PGC1a expression was highly associated with a shorter overall survival time in patients with BC. High concentrations of palmitic acid (PA) promoted PGC1a expression and increased BC cell proliferation.