Abnormal lipid metabolism plays crucial roles in the development of cancer. Spindlin 1 (SPIN1) involving the process of spindle organization and chromosomal stability serves as an important player in the carcinogenesis. In this study, we try to identify the new function of SPIN1 in lipid metabolism of liver cancer. Tissue microarray showed that 75% (60/80) of hepatocellular carcinoma (HCC) tissues were positive for SPIN1, which was highly expressed in clinical HCC samples and positively associated with malignancy of HCC. Strikingly, SPIN1 could modulate abnormal lipid metabolism by increasing intracellular triglycerides, cholesterols, and lipid droplets in hepatoma cells, which could remarkably enhance the proliferation of hepatoma cells. Mechanistically, SPIN1 up-regulated FASN in hepatoma cells. SPIN1 co-activated transcriptional factor SREBP1c in the promoter of FASN through interaction with SREBP1c. Moreover, SPIN1 promoted the growth of liver cancer in vitro and in vivo and the levels of intracellular triglycerides, cholesterols and lipid droplets were increased in the tumor tissues from mice. In conclusion, SPIN1 modulates abnormal lipid metabolism and enhances growth of liver cancer through SREBP1c-triggered FASN signaling. Therapeutically, SPIN1 may serve as a novel target for HCC.
Keywords: FASN; Lipid metabolism; Liver cancer; SPIN1; SREBP1c.
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