Investigating the crosstalk of glucose metabolism and c-met pathway in hepatocellular carcinoma

Objective: In the context of this study, investigating the crosstalk of c-Met and insulin receptor under high glucose and insulin induction and the effect of this interaction on HCC cell biology is aimed. Methods: Immunoblotting and immunoflourescence, co-immunoprecipitation, quantitative polymerase chain reaction, real time cell adhesion and proliferation, motility and invasion analysis, Seahorse cell metabolism assay and metastasis analysis in zebrafish xenograft model were used in this study. Results: c-Met expression and activation are elevated under high glucose and insulin conditions. Besides downstream molecules are also activated as a result. HCC cell metabolism is affected when c-Met is inhibited. The interaction of c-Met with insulin receptor is increased when cells are treated with high glucose and insulin. Cell adhesion, proliferation, motility and invasion are increased with high glucose and insulin induction. The effects are reversed with c-Met inhibition and even more together with insulin receptor inhibition. Conclusion: It has been shown for the first time that c-Met and insulin receptor are interacting as a result of high glucose and insulin induction, which helps HCC cells to gain more metastatic abilities. However these effects are suppressed when both receptors are inhibited, and both receptors are suggested as valuable therapeutic targets especially in HCC developed in the background of obesity.