MET/SRC/EGFR complex formation induced by cetuximab is involved in resistance to cetuximab. (A,B) Whole-cell extracts from Caco-2 cells and DiFi cells treated or untreated with 10 μg/mL cetuximab for 48 h in 2% FBS medium were immunoprecipitated with anti-MET antibody. The immunoprecipitates were probed with MET, SRC and EGFR antibodies. Input represents cell lysates that were not subjected to immunoprecipitation, and control immunoprecipitation was done using IgG mouse; (C,D) Caco-2 cells were treated with cetuximab or combination with SRC inhibitors (PP2 or Dasatinib) or PHA-665752 for 48 h. The effect on MET/SRC/EGFR complex was analysed by Western blotting using immunoprecipitation with anti-MET or anti-SRC antibodies; (E) Heterodimerization of MET and EGFR was detected by Duolink in situ PLA (blue, nuclear; red dot, MET-EGFR heterodimer) when exposed to 10 μg/mL cetuximab or combined with Dasatinb or PHA-665752 for 48 h in Caco-2 cells.