title: Ligation of CM1 enhances apoptosis of lung cancer cells through different             mechanisms in conformity with EGFR mutation.
abstract: Although remarkable developments in lung cancer treatments have been made,             lung cancer remains the leading cause of cancer mortality worldwide. Epidermal             growth factor receptor (EGFR) is occasionally mutated in non-small cell lung cancer             and heterogeneity in treatment response results from different EGFR mutations.             In the present study, we found that centrocyte/centroblast marker 1 (CM1), previously             reported as a possible apoptosis inducer of B lymphoma cells, is expressed on             both A549 with wild‑type EGFR and HCC827 with mutant EGFR lung cancer cells. Ligation             of CM1 with anti-CM1 mAb enhanced apoptosis in both lung cancer cell lines through             generation of reactive oxygen species (ROS) and disruption of mitochondrial membrane             potential, however, the signaling mechanisms differed from each other. Further             studies to investigate the signaling mechanisms identified that ligation of CM1‑induced             apoptosis in A549 cell involved FasL expression, caspase-8, ERK1/2 and Akt kinase,             whereas apoptosis of HCC827 cells was induced through caspase-9, JNK and c-jun‑dependent             pathways. Taken together, we suggest that CM1 could be developed as a therapeutic             target of lung cancer regardless of EGFR mutation status.
authors.affiliation: Department of Internal Medicine, Inje University Busan Paik Hospital,                     Busan 614-735, Republic of Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Ga Bin
authors.initials: GB
authors.lastname: Park
authors.forename: Yeong Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: V Courtney
authors.initials: VC
authors.lastname: Broaddus
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Hur
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D018858:Germinal Center / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D017382:Reactive Oxygen Species; C585430:centrocyte centroblast marker 1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors