Lung injury and cancer: Mechanistic insights into ceramide and EGFR signaling under cigarette smoke.
Cigarette smoke has been connected to an array of chronic lung diseases and is a major source of morbidity and mortality. Active smoking is responsible for approximately 90% of lung cancer cases. In addition, cigarette smoke is associated with other chronic pulmonary diseases such as pulmonary edema, chronic bronchitis, and pulmonary emphysema, the last two also termed chronic obstructive pulmonary disease (COPD). Lung cancer and COPD are developed very frequently in chronic cigarette smokers. It has been known for some time that lung cancer incidence increases in patients with COPD. Even the existence of some low-grade emphysema without noticeable airflow obstruction is associated with significantly elevated risk of lung cancer. These recent clinical insights demand new thinking and exploration of novel mechanistic studies to fully understand these observations. Lung injury and repair involve cell death and hyperplasia of airway epithelial cells and infiltration of inflammatory cells. All of these occur simultaneously. The mechanisms of cell death and hyperplasia in the lung constitute two sides of the coin of lung injury and repair. However, most molecular studies in airway epithelial cells center on the mechanism(s) of either cell growth and proliferation or cell death and the ceramide-generating machinery that drives aberrant induction of apoptotic cell death. Very few address both sides of the coin as an outcome of cigarette smoke exposure, which is the focus of this review.
Goldkorn
Tzipora
T
University of California, Davis, 95616, USA. ttgoldkorn@ucdavis.edu
Filosto
Simone
S
D000818:Animals; D017209:Apoptosis; D002518:Ceramides / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D055370:Lung Injury / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D015398:Signal Transduction / Q000502:physiology*; D012907:Smoking / Q000378:metabolism*
D002518:Ceramides; C512478:EGFR protein, human; D066246:ErbB Receptors