IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12961.html
   My bibliography  Save this article

The tobacco-specific carcinogen-operated calcium channel promotes lung tumorigenesis via IGF2 exocytosis in lung epithelial cells

Author

Listed:
  • Hye-Jin Boo

    (Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University)

  • Hye-Young Min

    (Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University
    Graduate School of Convergence Science and Technology, Seoul National University)

  • Hyun-Ji Jang

    (Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University)

  • Hye Jeong Yun

    (Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University)

  • John Kendal Smith

    (The University of Texas M.D. Anderson Cancer Center)

  • Quanri Jin

    (The University of Texas M.D. Anderson Cancer Center)

  • Hyo-Jong Lee

    (The University of Texas M.D. Anderson Cancer Center)

  • Diane Liu

    (The University of Texas M.D. Anderson Cancer Center)

  • Hee-Seok Kweon

    (Korea Basic Science Institute)

  • Carmen Behrens

    (The University of Texas M.D. Anderson Cancer Center)

  • J. Jack Lee

    (The University of Texas M.D. Anderson Cancer Center)

  • Ignacio I. Wistuba

    (The University of Texas M.D. Anderson Cancer Center
    The University of Texas M.D. Anderson Cancer Center)

  • Euni Lee

    (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)

  • Waun Ki Hong

    (The University of Texas M.D. Anderson Cancer Center)

  • Ho-Young Lee

    (Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University
    Graduate School of Convergence Science and Technology, Seoul National University
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)

Abstract

Nicotinic acetylcholine receptors (nAChRs) binding to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces Ca2+ signalling, a mechanism that is implicated in various human cancers. In this study, we investigated the role of NNK-mediated Ca2+ signalling in lung cancer formation. We show significant overexpression of insulin-like growth factors (IGFs) in association with IGF-1R activation in human preneoplastic lung lesions in smokers. NNK induces voltage-dependent calcium channel (VDCC)-intervened calcium influx in airway epithelial cells, resulting in a rapid IGF2 secretion via the regulated pathway and thus IGF-1R activation. Silencing nAChR, α1 subunit of L-type VDCC, or various vesicular trafficking curators, including synaptotagmins and Rabs, or blockade of nAChR/VDCC-mediated Ca2+ influx significantly suppresses NNK-induced IGF2 exocytosis, transformation and tumorigenesis of lung epithelial cells. Publicly available database reveals inverse correlation between use of calcium channel blockers and lung cancer diagnosis. Our data indicate that NNK disrupts the regulated pathway of IGF2 exocytosis and promotes lung tumorigenesis.

Suggested Citation

  • Hye-Jin Boo & Hye-Young Min & Hyun-Ji Jang & Hye Jeong Yun & John Kendal Smith & Quanri Jin & Hyo-Jong Lee & Diane Liu & Hee-Seok Kweon & Carmen Behrens & J. Jack Lee & Ignacio I. Wistuba & Euni Lee &, 2016. "The tobacco-specific carcinogen-operated calcium channel promotes lung tumorigenesis via IGF2 exocytosis in lung epithelial cells," Nature Communications, Nature, vol. 7(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12961
    DOI: 10.1038/ncomms12961
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12961
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12961?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12961. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.