title: Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer.
abstract: Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-β-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies.
authors: Department of Thoracic and Cardiovascular Surgery, University of Toyama, Toyama 930-0194, Japan.
authors: Masayoshi
authors: M
authors: Toge
authors: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors: Satoru
authors: S
authors: Yokoyama
authors: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors: Shinichiro
authors: S
authors: Kato
authors: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors: Hiroaki
authors: H
authors: Sakurai
authors: Department of Thoracic and Cardiovascular Surgery, University of Toyama, Toyama 930-0194, Japan.
authors: Kazutaka
authors: K
authors: Senda
authors: Department of Thoracic and Cardiovascular Surgery, University of Toyama, Toyama 930-0194, Japan.
authors: Yoshinori
authors: Y
authors: Doki
authors: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors: Yoshihiro
authors: Y
authors: Hayakawa
authors: Department of Thoracic and Cardiovascular Surgery, University of Toyama, Toyama 930-0194, Japan.
authors: Naoki
authors: N
authors: Yoshimura
authors: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors: Ikuo
authors: I
authors: Saiki
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: C096816:BCL2-related protein A1; C579095:MCL1 protein, human; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D002945:Cisplatin