Knockdown of MACC1 expression attenuates colorectal cancer cell glucose metabolism by suppressing GLUT4 membrane translocation.

BackgroundMetastasis-associated in colon cancer-1 (MACC1) is a novel oncogene involved in the growth and metastasis of tumors, which is overexpression in various tumors. MACC1 could promote the growth, invasion, and metastasis of colorectal cancer (CRC) by activating the HGF/MET signaling pathway in vivo. It has been confirmed that MACC1 mainly promotes the Warburg effect in gastric cancer cells through the PI3 K/AKT signaling pathway.ObjectiveHere, we mainly investigated the association between MACC1 and the glycolysis process in CRC cells.MethodsThe expression of MACC1 in CRC and its relationship with the patient's survival were analyzed by TCGA database. We used different concentrations of glucose medium to culture HT-29 and HCT-116 with or without siMACC1. Cell Counting Kit-8 assay was used to detect cell proliferation. The content of lactic acid and glucose in cells was examined by enzyme-linked immunosorbent assay, and extracellular acidification rate was also determined with Seahorse XFe96 Extracellular Flux Analyzer. Western blot was used to detect the protein expressions related to glycolysis. Immunofluorescence was conducted to observe the expression and distribution of GLUT4.ResultsIn this study, we observed that MACC1 was highly expressed in CRC and negatively correlated with the survival of patients. The expression of glycolysis related enzymes was significantly increased under the stimulation of different concentrations of glucose in HT-29 and HCT-116 cells. However, MACC1 knockdown could significantly reduce high glucose-induced the expressions of glycolysis-related enzymes. Besides, MACC1 knockdown could decrease the content of glucose and lactate, and inhibit glycolytic function in HT-29 and HCT-116 cells. Moreover, the expression of GLUT4 was significantly decreased in the two cell lines treated by 4.5 g/L or 9.0 g/L glucose with MACC1 knockdown. Additionally, MACC1 knockdown could inhibit high glucose-induced membrane translocation of GLUT4.ConclusionsMACC1 knockdown can attenuate glucose metabolism by inhibiting the membrane translocation of GLUT4 in CRC cells.