@article{TEXTUAL,
      recid = {10718},
      author = {Lennon, Frances E. and Mirzapoiazova, Tamara and  Mambetsariev, Bolot and Poroyko, Valeriy A. and Salgia,  Ravi and Moss, Jonathan and Singleton, Patrick A.},
      title = {The Mu Opioid Receptor Promotes Opioid and Growth  Factor-Induced Proliferation, Migration and Epithelial  Mesenchymal Transition (EMT) in Human Lung Cancer},
      journal = {PLOS ONE},
      address = {2014-03-24},
      number = {TEXTUAL},
      abstract = {<p>Recent epidemiologic studies implying differences in  cancer recurrence based on anesthetic regimens raise the  possibility that the mu opioid receptor (MOR) can influence  cancer progression. Based on our previous observations that  overexpression of MOR in human non-small cell lung cancer  (NSCLC) cells increased tumor growth and metastasis, this  study examined whether MOR regulates growth factor receptor  signaling and epithelial mesenchymal transition (EMT) in  human NSCLC cells. We utilized specific siRNA, shRNA,  chemical inhibitors and overexpression vectors in human  H358 NSCLC cells that were either untreated or treated with  various concentrations of DAMGO, morphine, fentanyl, EGF or  IGF. Cell function assays, immunoblot and  immunoprecipitation assays were then performed. Our results  indicate MOR regulates opioid and growth factor-induced EGF  receptor signaling (Src, Gab-1, PI3K, Akt and STAT3  activation) which is crucial for consequent human NSCLC  cell proliferation and migration. In addition, human NSCLC  cells treated with opioids, growth factors or MOR  overexpression exhibited an increase in snail, slug and  vimentin and decrease ZO-1 and claudin-1 protein levels,  results consistent with an EMT phenotype. Further, these  effects were reversed with silencing (shRNA) or chemical  inhibition of MOR, Src, Gab-1, PI3K, Akt and STAT3  (p<0.05). Our data suggest a possible direct effect of MOR  on opioid and growth factor-signaling and consequent  proliferation, migration and EMT transition during lung  cancer progression. Such an effect provides a plausible  explanation for the epidemiologic findings.</p>},
      url = {http://knowledge.uchicago.edu/record/10718},
}