title: Nicotinamide N-methyltransferase in non-small cell lung cancer: promising results for targeted anti-cancer therapy.
abstract: Lung cancer, predominantly non-small cell lung cancer (NSCLC), is currently the most common cause of malignancy-related death in the world. Despite advances in both detection and treatment, its incidence rate is still increasing. Therefore, effective strategies for early detection as well as molecular therapeutic targets are urgently needed. We focused on the enzyme nicotinamide N-methyltransferase (NNMT). NNMT expression levels were investigated in tumor, tumor-adjacent, and surrounding tissue samples of 25 patients with NSCLC by Real-Time PCR, Western blot analysis, and catalytic activity assay. NNMT enzyme activity in NSCLC was then correlated with clinicopathological characteristics. Results obtained showed NNMT upregulation (mRNA and protein) in tumor compared with both tumor-adjacent and surrounding tissue. Moreover, NSCLC displayed significantly higher activity levels than those determined in both tumor-adjacent and surrounding tissue. Interestingly, both tumor-adjacent and surrounding tissue samples of unfavorable cases (N+) seem to display higher activity levels than those of favorable NSCLCs (N0). The present work shows a marked increase of NNMT enzyme activity in NSCLC and suggests that normal-looking tissue of unfavorable cases seems to change toward cancer. Further studies may establish whether NNMT could represent a target for an effective anti-cancer therapy.
authors.affiliation: Sezione di Biochimica, Dipartimento di Scienze Cliniche Specialistiche e Odontostomatologiche, Università Politecnica delle Marche, Via Ranieri 65, 60131, Ancona, Italy, davide_sartini@libero.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Sartini
authors.forename: Stefano
authors.initials: S
authors.lastname: Morganti
authors.forename: Elena
authors.initials: E
authors.lastname: Guidi
authors.forename: Corrado
authors.initials: C
authors.lastname: Rubini
authors.forename: Antonio
authors.initials: A
authors.lastname: Zizzi
authors.forename: Rachela
authors.initials: R
authors.lastname: Giuliante
authors.forename: Valentina
authors.initials: V
authors.lastname: Pozzi
authors.forename: Monica
authors.initials: M
authors.lastname: Emanuelli
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D050903:Nicotinamide N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D050903:Nicotinamide N-Methyltransferase