Found programs: Tianchi Talent Project for Young Doctors in Xinjiang Uygur Autonomous Region (No. 2025TCYCHYS); Natural Science Foundation of Xinjiang Uygur Autonomous Region (No. 2021D01C185)
Authors：Huo Yishan 1, Duan Xiangbing 1, Xu Xiaohui 1, Li Tao 2, Ma Xiumin 1
Keywords：S100A2; colorectal cancer; fructose metabolism; facilitated glucose transporter member 5; ketohexokinase
DOI：专辑：医药卫生科技
〔Abstract〕 To investigate the role of calcium-binding protein S100A2 in colorectal cancer (CRC) progression and its association with fructose metabolism in CRC cells. Methods Differential expression of S100A2 between CRC patients and healthy individuals was analyzed using the GEPIA2 tumor database. Western blot and qRT-PCR were performed to compare S100A2 expression levels in CRC cell lines (HCT116, SW480, Caco-2) and normal human colonic epithelial cells (NCM460). Immunohistochemical staining was conducted to assess S100A2 expression in CRC tissues and adjacent non-tumor tissues. S100A2-knockdown stable CRC cell lines and negative control cell lines were established via lentiviral transduction. Functional assays, including CCK-8, wound healing and Transwell experiments were utilized to evaluate the effects of S100A2 downregulation on CRC cell proliferation, migration, and invasion. Western blot and immunofluorescence staining were employed to analyze the impact of S100A2 knockdown on the expression levels of fructose transporter 5 (GLUT5) and ketohexokinase (KHK). Intracellular fructose concentration was measured using a fructose assay kit. A nude mouse CRC xenograft model was established using S100A2-knockdown HCT116 cell lines to investigate the role of S100A2 in tumor proliferation in vivo. Tumor tissues from the xenografted mice were analyzed by Western blot and immunofluorescence staining to evaluate the expression levels of GLUT5 and KHK. Results S100A2 expression was significantly elevated in CRC patients compared with healthy individuals. All three CRC cell lines exhibited markedly higher S100A2 expression than normal colonic epithelial cells. S100A2 knockdown significantly inhibited CRC cell proliferation, migration, and invasion capacities. Downregulation of S100A2 suppressed the expression of fructose metabolism-related proteins GLUT5 and KHK, accompanied by reduced cellular fructose uptake. In vivo experiments demonstrated that S100A2 knockdown effectively inhibited tumor growth and decreased GLUT5/KHK expression in xenograft tissues. Conclusion Downregulation of S100A2 inhibits CRC progression by modulating fructose metabolism in CRC cells.