S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

Abstract Background Glucose metabolism transformation plays critical role in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. S100A4 has been identified as an oncogene in a variety of cancers. However, its role in the cancer cell glucose reprogramming has been seldom reported. The aim of this study was to examine the role of S100A4 in aerobic glycolysis in colorectal cancer (CRC). Methods We investigated S100A4 expression in 224 cases of primary CRC and matched normal colonic tissue specimens, and explored the underlying mechanisms of altered S100A4 expression as well as the impact of this altered expression on CRC growth and glycolysis using in vitro and animal models of CRC. Results S100A4 was more highly expressed in CRC tissues than in the adjacent normal tissues (59.4% vs 17.4%, P <0.05). Higher S100A4 expression was associated with advanced node stage ( P =0.018) and larger tumor size ( P =0.035). A Cox proportional hazards model suggested that S100A4 expression was an independent prognostic factor for both OS (HR: 3.967, 95%CI: 1.919-8.200, P <0.001) and DFS (HR: 4.350, 95%CI: 2.264-8.358, P <0.001) in CRC after surgery. Experimentally, silencing S100A4 expression significantly decreased the growth and glycolysis rate of CRC both in vitro and in vivo . Mechanically, S100A4 could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element–luciferase activity in CRC cells. Conclusions These results disclose a novel role for S100A4 in reprogramming the metabolic process in CRC by affecting the HIF-1α activity and provide potential prognostic predictors for CRC.