HIF1A and neoplasm: GSEA further revealed that arecoline significantly upregulated key profibrotic and tumor-associated pathways, including those related to adherens junctions, tight junctions, focal adhesion, TGF-β signaling, EGFR tyrosine kinase inhibitor resistance, HIF-1 signaling, MAPK signaling, and microRNAs in cancer, all of which contribute to tumor progression and fibrosis (Fig. 3B).