Fig 2: AXL and MET expression was positively associated with HCC. (A) AXL expression was positively correlated with HCC tissues and cirrhosis in the analysis of the Oncomine database (https://www.oncomine.com/). (B) MET expression was significantly upregulated in HCC tissues compared with normal tissues according to the analysis of data in the Oncomine database. (C) Kaplan–Meier plot presenting the association of AXL with HCC. High expression of AXL was associated with poor overall survival in patients with HCC. (D) Kaplan–Meier plot presenting the association of MET with overall survival in patients with HCC. High expression of MET was associated with poor progression-free survival and relapse-free survival in patients with HCC.

Fig 3: MET and AXL signaling involved in Galectin-1-mediated sorafenib resistance and ferroptosis in HCC. (A) Galectin-1-knocked-down Huh-7/SR (Huh-7/SR/shGal#23 and #24) and control (Huh-7/SR/shCtrl) cells were analyzed for RTK expression (EGFR, MET, AXL, and insulin receptor) through Western blotting. Huh-7/SR cells were treated with an MET inhibitor and AXL inhibitor R428 for 48 hr. Analysis of Galectin-1, AXL, and phospho-AXL expression (B upper panel) and MET and phospho-MET expression (C upper panel) were performed using Western blotting. Cell viability of Huh-7/SR cells cotreated with 20 µM of sorafenib and AXL (B lower panel) or an MET inhibitor (C lower panel) for 48 h. Galectin-1 overexpression after treatment with the MET inhibitor and AXL inhibitor R428 for 48 h. Analysis of AXL and phospho-AXL expression (D upper panel) and MET and phospho-MET expression (E upper panel) by using Western blotting. Cell viability of Galectin-1- overexpressing cells cotreated with 20 µM of sorafenib and AXL (D lower panel) or a MET inhibitor (E lower panel) for 48 h. (F) Oct-4, Nanog, SOX-2, and KLF4 mRNA expression determined using qRT-PCR in Galectin-1-overexpressing cells treated with an MET inhibitor and an AXL inhibitor R428. Western blot analysis was used to detect AXL, phospho-AXL, GPX4, and ferritin heavy chain 1 expression in cells cotreated with 20 µM of sorafenib and an (G) AXL inhibitor or (H) MET inhibitor. Data are presented as means ± standard deviations. **P < 0.01, and ***P < 0.001 (Student’s t test).