Targeting KITENIN signaling in cancer progression and therapeutic resistance: mechanistic insights and future directions

Abstract KITENIN (KAI1 C-terminal interacting tetraspanin) has emerged as a critical oncogenic mediator involved in tumor initiation, progression, metastasis, and therapeutic resistance. Initially identified through its interaction with the metastasis suppressor KAI1/CD82, KITENIN activates c-Jun N-terminal kinase (JNK) signaling and AP-1–dependent transcription, thereby driving epithelial–mesenchymal transition (EMT), cytoskeletal remodeling, and invasive behavior. Aberrant KITENIN expression has been reported in diverse solid tumors, including colorectal, gastric, hepatocellular carcinomas, and glioblastoma, where it correlates with aggressive phenotypes and poor prognosis. Preclinical studies