title: Overexpression of muscarinic receptor 3 promotes metastasis and predicts poor prognosis in non-small-cell lung cancer.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer development, but the mechanism is not fully understood. Muscarinic receptor 3 (M3R) has been found to be involved in the progression of small-cell lung cancer and the pathological process of COPD. We hypothesized that M3R may contribute to lung cancer development, especially in patients with COPD.
  
  
  METHODS
  The correlation between M3R expression and clinical features of non-small-cell lung cancer (NSCLC) was evaluated in 148 paraffin-embedded archived NSCLC specimens with the use of immunohistochemistry. M3R agonist and siRNA treatments were used to study the role of M3R in NSCLC cell lines. Western blotting and zymography were used to examine the impact of M3R on the PI3K/Akt/matrix metalloproteinase 9 signaling pathway.
  
  
  RESULTS
  The expression of M3R in NSCLC was significantly increased and correlated with tumor metastasis and poor survival of NSCLC patients. NSCLC patients with COPD showed higher expression of M3R than those without COPD (p = 0.0014). Moreover, M3R expression was inversely related to percent forced expiratory volume in 1 second (r = 0.7017, p < 0.0001) and forced expiratory volume in 1 second /forced vital capacity (r = 0.5057, p < 0.0001), but positively related to smoking history. Down-regulation of M3R resulted in the inhibition of migration and invasion ability of NSCLC cell lines A549 and L78. Furthermore, M3R enhanced the expression and activity of matrix metalloproteinase 9 through PI3K/Akt, which promoted the migration and invasion of NSCLC cell lines.
  
  
  CONCLUSIONS
  Our results suggest that overexpression of M3R in NSCLC promotes the progression of NSCLC, which could contribute to lung cancer development in COPD patients. M3R could be another pharmacological target in lung cancer, especially in COPD patients.
authors.affiliation: *Respiratory Department, The First Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China; †Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; and ‡Respiratory Department, Nanchang Hospital of Integrative Traditional Chinese and Western Medicine, Nanchang, Jiangxi, People's Republic of China.
authors.forename: Gengpeng
authors.initials: G
authors.lastname: Lin
authors.forename: Longhua
authors.initials: L
authors.lastname: Sun
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.forename: Yubiao
authors.initials: Y
authors.lastname: Guo
authors.forename: Canmao
authors.initials: C
authors.lastname: Xie
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D043587:Receptor, Muscarinic M3