ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer

Figure 4 Intercellular adhesion molecule 2 knockdown enhances pleiotrophin expression and 5-fluorouracil resistance by activating the TGF-β/Smad signaling in gastric cancer. A: The relationship between the TGF-β signaling pathway and intercellular adhesion molecule 2 (ICAM2) in gene set enrichment analysis based on RNA-seq data; B: Kyoto Encyclopedia of Genes and Genomes pathway analysis showing enrichment of the TGF-β pathway; C: Western blot analysis of TGF-β/Smad2/3 pathway proteins and pleiotrophin (PTN) expression in the indicated cells; D: Immunoblotting of nuclear P-Smad2/3 levels in the indicated cells; E: Treatment with LY2157299 reversed the effects of ICAM2 knockdown on TGF-β/Smad2/3 pathway proteins and PTN expression; F-H: Cytotoxicity, flow cytometry, and apoptosis-related protein analysis of ICAM2-knockdown gastric cancer cells treated with DMSO or LY2157299. ^aP < 0.001; ^bP < 0.01. PTN: Pleiotrophin; 5-FU: 5-fluorouracil; KEGG: Kyoto Encyclopedia of Genes and Genomes; ICAM2: Intercellular adhesion molecule 2; IC₅₀: Half-maximal inhibitory concentration.