Nicotine-Mediated Cell Proliferation and Tumor Progression in Smoking-Related Cancers

被引:272
作者
Schaal, Courtney [1 ]
Chellappan, Srikumar P. [1 ]
机构
[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, Tampa, FL 33612 USA
关键词
RECEPTOR SUBUNIT GENES; GROWTH-FACTOR RECEPTOR; LUNG-CANCER; ACETYLCHOLINE-RECEPTOR; TOBACCO CARCINOGEN; SIGNALING PATHWAYS; EPITHELIAL-CELLS; DOWN-REGULATION; CYCLIN D1; ALPHA-7-NICOTINIC RECEPTOR;
D O I
10.1158/1541-7786.MCR-13-0541
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tobacco smoke contains multiple classes of established carcinogens including benzo(a) pyrenes, polycyclic aromatic hydrocarbons, and tobacco-specific nitrosamines. Most of these compounds exert their genotoxic effects by forming DNA adducts and generation of reactive oxygen species, causing mutations in vital genes such as K-Ras and p53. In addition, tobacco-specific nitrosamines can activate nicotinic acetylcholine receptors (nAChR) and to a certain extent beta-adrenergic receptors (beta-AR), promoting cell proliferation. Furthermore, it has been demonstrated that nicotine, the major addictive component of tobacco smoke, can induce cell-cycle progression, angiogenesis, and metastasis of lung and pancreatic cancers. These effects occur mainly through the alpha 7-nAChRs, with possible contribution from the beta-ARs and/or epidermal growth factor receptors. This review article will discuss the molecular mechanisms by which nicotine and its oncogenic derivatives such as 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone and N-nitrosonornicotine induce cell-cycle progression and promote tumor growth. A variety of signaling cascades are induced by nicotine through nAChRs, including the mitogen-activated protein kinase/ extracellular signal-regulated kinase pathway, phosphoinositide 3-kinase/AKT pathway, and janus-activated kinase/STAT signaling. In addition, studies have shown that nAChR activation induces Src kinase in a beta-arrestin-1-dependent manner, leading to the inactivation of Rb protein and resulting in the expression of E2F1-regulated proliferative genes. Such nAChR-mediated signaling events enhance the proliferation of cells and render them resistant to apoptosis induced by various agents. These observations highlight the role of nAChRs in promoting the growth and metastasis of tumors and raise the possibility of targeting them for cancer therapy. (C) 2014 AACR.
引用
收藏
页码:14 / 23
页数:10
相关论文
共 92 条
  • [1] Cooperative Regulation of Non-Small Cell Lung Carcinoma by Nicotinic and Beta-Adrenergic Receptors: A Novel Target for Intervention
    Al-Wadei, Hussein A. N.
    Al-Wadei, Mohammed H.
    Schuller, Hildegard M.
    [J]. PLOS ONE, 2012, 7 (01):
  • [2] Inhibition of the Nicotinic Acetylcholine Receptors by Cobra Venom α-Neurotoxins: Is There a Perspective in Lung Cancer Treatment?
    Alama, Angela
    Bruzzo, Cristina
    Cavalieri, Zita
    Forlani, Alessandra
    Utkin, Yuri
    Casciano, Ida
    Romani, Massimo
    [J]. PLOS ONE, 2011, 6 (06):
  • [3] Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1
    Amos, Christopher I.
    Wu, Xifeng
    Broderick, Peter
    Gorlov, Ivan P.
    Gu, Jian
    Eisen, Timothy
    Dong, Qiong
    Zhang, Qing
    Gu, Xiangjun
    Vijayakrishnan, Jayaram
    Sullivan, Kate
    Matakidou, Athena
    Wang, Yufei
    Mills, Gordon
    Doheny, Kimberly
    Tsai, Ya-Yu
    Chen, Wei Vivien
    Shete, Sanjay
    Spitz, Margaret R.
    Houlston, Richard S.
    [J]. NATURE GENETICS, 2008, 40 (05) : 616 - 622
  • [4] Estimating the Risks and Benefits of Nicotine Replacement Therapy for Smoking Cessation in the United States
    Apelberg, Benjamin J.
    Onicescu, Georgiana
    Avila-Tang, Erika
    Samet, Jonathan M.
    [J]. AMERICAN JOURNAL OF PUBLIC HEALTH, 2010, 100 (02) : 341 - 348
  • [5] ABSORPTION AND METABOLISM OF NICOTINE FROM CIGARETTES
    ARMITAGE, AK
    DOLLERY, CT
    GEORGE, CF
    HOUSEMAN, TH
    LEWIS, PJ
    TURNER, DM
    [J]. BRITISH MEDICAL JOURNAL, 1975, 4 (5992) : 313 - 316
  • [6] Receptor-mediated tobacco toxicity:: cooperation of the Ras/Raf-1/MEK1/ERK and JAK-2/STAT-3 pathways downstream of α7 nicotinic receptor in oral keratinocytes
    Arredondo, Juan
    Chernyavsky, Alexander I.
    Jolkovsky, David L.
    Pinkerton, Kent E.
    Grando, Sergei A.
    [J]. FASEB JOURNAL, 2006, 20 (12) : 2093 - 2101
  • [7] Baldi Alfonso, 2011, Patholog Res Int, V2011, P605042, DOI 10.4061/2011/605042
  • [8] Nicotine activates cell-signaling pathways through muscle-type and neuronal nicotinic acetylcholine receptors in non-small cell lung cancer cells
    Carlisle, Diane L.
    Liu, Xuwan
    Hopkins, Toni M.
    Swick, Michelle C.
    Dhir, Rajiv
    Siegfried, Jill M.
    [J]. PULMONARY PHARMACOLOGY & THERAPEUTICS, 2007, 20 (06) : 629 - 641
  • [9] Smoking Cessation: An Integral Part of Lung Cancer Treatment
    Cataldo, Janine K.
    Dubey, Sarita
    Prochaska, Jodi J.
    [J]. ONCOLOGY, 2010, 78 (5-6) : 289 - 301
  • [10] Targeting α7-nicotinic receptor for the treatment of pleural mesothelioma
    Catassi, Alessia
    Paleari, Laura
    Servent, Denis
    Sessa, Fausto
    Dominioni, Lorenzo
    Ognio, Emanuela
    Cilli, Michele
    Vacca, Paola
    Mingari, Mariacristina
    Gaudino, Giovanni
    Bertino, Pietro
    Paolucci, Massimo
    Calcaterra, Andrea
    Cesario, Alfredo
    Granone, Pierluigi
    Costa, Roberta
    Ciarlo, Monica
    Alama, Angela
    Russo, Patrizia
    [J]. EUROPEAN JOURNAL OF CANCER, 2008, 44 (15) : 2296 - 2311