HSF1: a mediator in metabolic alteration of hepatocellular carcinoma cells in cross-talking with tumor-associated macrophages.

Recently, heat shock transcription factor 1 (HSF1) is observed to be involved in the process of cellular metabolism in cancer. However, the roles of HSF1 in the metabolic alteration of hepatocellular carcinoma (HCC) in tumor microenvironment remain elusive. Here, HCC cells were co-cultured with tumor-associated macrophages (TAM). The levels of glucose uptake, the lactate release, reactive oxygen species (ROS) and mtDNA content were measured by the associated Kits; all detected protocols were correspondingly according to the manufacturers' instructions. Recombinant lentiviruses with shRNA against HSF1 and MCT4 were transfected into HCC cells or TAMs. Western blot analysis was conducted to detect the relative levels of HSF1, MCT1 and MCT4 proteins. CCK-8 assay was utilized to assess cell proliferation. Based on the co-culture system with HCC cells and TAMs, metabolic alteration of HCC cells after co-culture with TAMs was observed. Furthermore, glucose consumption rate, lactate production rate and intercellular ROS level were decreased, while the copy number of mtDNA was increased in HSF1-knockdown HCC cells. Besides, metabolic crosstalk between HCC cells and TAMs was induced by HSF1 not only in HCC cells but also in TAMs through regulating individually MCT1 and MCT4 expressions. To the best of our knowledge, this is an important study to demonstrate the roles of HSF1 in regulating metabolic alteration of HCC cells induced by TAMs, which implies the potential use of HSF1 as a target modulating malignant behaviors of HCC cells.