Fig. 8: Proposed model by which Dsg2 suppresses tumor formation in GBC.

a Dsg2 functions as a tumor suppressor through binding between the Dsg2 IL domain and cSrc SH2 domain. The EGFR-targeted therapy suppresses EGFR signaling pathway. b The loss of Dsg2 in GBC activates cSrc and promotes EGFR internalization, which induces resistance to EGFR-targeted therapy. c Combination therapy targeting both cSrc and EGFR is a promising therapeutic strategy for GBC patients with Dsg2 loss.