Ligation of CM1 enhances apoptosis of lung cancer cells through different mechanisms in conformity with EGFR mutation

Lee,Hyun-Kyung; Park,Ga  Bin; Kim,Yeong  Seok; Song,Hyunkeun; Broaddus,V.  Courtney; Hur,Dae  Young

doi:10.3892/ijo.2012.1731

Ligation of CM1 enhances apoptosis of lung cancer cells through different mechanisms in conformity with EGFR mutation

Authors:
- Hyun-Kyung Lee
- Ga Bin Park
- Yeong Seok Kim
- Hyunkeun Song
- V. Courtney Broaddus
- Dae Young Hur
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Affiliations: Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea, Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea, Lung Biology Center, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA
Published online on: December 7, 2012 https://doi.org/10.3892/ijo.2012.1731
Pages: 469-477
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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