Hepatocyte growth factor (HGF) from CAFs drives HCC stemness and chemoresistance through FRA1-dependent signaling, enhancing spheroid formation, upregulating stem cell markers (CD44/EpCAM), and conferring cisplatin and sorafenib resistance, as evidenced by multiple preclinical studies (56, 58, 59). This evidence concerns the gene CD44 and hepatocellular carcinoma.