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Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?
Ng Kee Kwong, Francois; Nicholson, Andrew G; Harrison, Celeste L; Hansbro, Philip M; Adcock, Ian M; Chung, Kian Fan.
Affiliation
  • Ng Kee Kwong F; Experimental Studies, National Heart and Lung Institute, Imperial College London, London, UK f.ng-kee-kwong@imperial.ac.uk.
  • Nicholson AG; Dept of Histopathology, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
  • Harrison CL; Experimental Studies, National Heart and Lung Institute, Imperial College London, London, UK.
  • Hansbro PM; Dept of Histopathology, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
  • Adcock IM; School of Biomedical Sciences and Pharmacy, Newcastle, Australia.
  • Chung KF; School of Biomedical Sciences and Pharmacy, Newcastle, Australia.
Eur Respir Rev ; 26(146)2017 Dec 31.
Article in En | MEDLINE | ID: mdl-29070578
ABSTRACT
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis.The functional state of the mitochondrion is dependent on the balance between its biogenesis and degradation (mitophagy). Dysfunctional mitochondria are a source of oxidative stress and inflammasome activation. In COPD, there is impaired translocation of the ubiquitin-related degradation molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in excessive dysfunctional mitochondria. We hypothesise that deranged pathways in mitochondrial biogenesis and mitophagy in COPD can account for the increased risk in carcinogenesis. To test this hypothesis, animal models exposed to cigarette smoke and developing emphysema and lung cancer should be developed. In the future, the use of mitochondria-based antioxidants should be studied as an adjunct with the aim of reducing the risk of COPD-associated cancer.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Transformation, Neoplastic / Carcinoma, Non-Small-Cell Lung / Pulmonary Disease, Chronic Obstructive / Mitochondrial Diseases / Lung / Lung Neoplasms / Mitochondria Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Humans Language: En Journal: Eur Respir Rev Year: 2017 Document type: Article Affiliation country: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Transformation, Neoplastic / Carcinoma, Non-Small-Cell Lung / Pulmonary Disease, Chronic Obstructive / Mitochondrial Diseases / Lung / Lung Neoplasms / Mitochondria Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Humans Language: En Journal: Eur Respir Rev Year: 2017 Document type: Article Affiliation country: United kingdom
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