L1 cell adhesion molecule and epidermal growth factor receptor activation confer cisplatin resistance in intrahepatic cholangiocarcinoma cells.

ABSTRACT

Intrahepatic cholangiocarcinoma (ICC) is refractory to conventional chemotherapy. We previously generated chemoresistant ICC (SCK(R)) cells and showed that AKT and ERK signaling conferred cisplatin resistance. Here, we report that epidermal growth factor receptor (EGFR) signaling and L1 cell adhesion molecule (L1CAM) conferred cisplatin resistance in SCK(R) cells in an additive fashion. Activation of EGFR connected to AKT and ERK signaling pathways may induce anti-apoptosis and promote cell proliferation, while L1CAM promoted cell proliferation by mainly activating ERK signaling. Inhibition of EGFR activation or L1ACM greatly sensitized the cells to cisplatin. EGFR and L1CAM may be important targets for ICC therapy.