Abstract:
:Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of EGFR TKIs. In this study, our data showed that chronic exposure to cigarette smoke extract (CSE) or tobacco smoke-derived carcinogen benzo[α]pyrene, B[α]P, but not nicotine-derived nitrosamine ketone (NNK), reduced the sensitivity of wild-type EGFR-expressing NSCLC cells to EGFR TKIs. Treatment with TKIs almost abolished EGFR tyrosine kinase activity but did not show an inhibitory effect on downstream Akt and ERK pathways in B[α]P-treated NSCLC cells. CSE and B[α]P transcriptionally upregulate c-MET and activate its downstream Akt pathway, which is not inhibited by EGFR TKIs. Silencing of c-MET reduces B[α]P-induced Akt activation. The CSE-treated NSCLC cells are sensitive to the c-MET inhibitor crizotinib. These findings suggest that cigarette smoke augments oncogene addiction to c-MET in NSCLC cells and that MET inhibitors may show clinical benefits for lung cancer patients with a smoking history.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Tu CY,Cheng FJ,Chen CM,Wang SL,Hsiao YC,Chen CH,Hsia TC,He YH,Wang BW,Hsieh IS,Yeh YL,Tang CH,Chen YJ,Huang WCdoi
10.1002/1878-0261.12193subject
Has Abstractpub_date
2018-05-01 00:00:00pages
705-723issue
5eissn
1574-7891issn
1878-0261journal_volume
12pub_type
杂志文章abstract::Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated ...
journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
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pub_type: 临床试验,杂志文章
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journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
pub_type: 杂志文章
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