title: 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.
authors.affiliation: Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Hyunho
authors.initials: H
authors.lastname: Yoon
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Dong Gwang
authors.initials: DG
authors.lastname: Lee
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Sang Seok
authors.initials: SS
authors.lastname: Koh
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Hong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D039842:Neural Cell Adhesion Molecule L1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D039842:Neural Cell Adhesion Molecule L1; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002945:Cisplatin