Department of Psychiatry, Brudnick Neuropsychiatric Research Institute; Tapper Lab; Gardner Lab
Cellular and Molecular Physiology | Neoplasms | Neuroscience and Neurobiology
Ion channels modulate ion flux across cell membranes, activate signal transduction pathways, and influence cellular transport-vital biological functions that are inexorably linked to cellular processes that go awry during carcinogenesis. Indeed, deregulation of ion channel function has been implicated in cancer-related phenomena such as unrestrained cell proliferation and apoptotic evasion. As the prototype for ligand-gated ion channels, nicotinic acetylcholine receptors (nAChRs) have been extensively studied in the context of neuronal cells but accumulating evidence also indicate a role for nAChRs in carcinogenesis. Recently, variants in the nAChR genes CHRNA3, CHRNA5, and CHRNB4 have been implicated in nicotine dependence and lung cancer susceptibility. Here, we silenced the expression of these three genes to investigate their function in lung cancer. We show that these genes are necessary for the viability of small cell lung carcinomas (SCLC), the most aggressive type of lung cancer. Furthermore, we show that nicotine promotes SCLC cell viability whereas an alpha3beta4-selective antagonist, alpha-conotoxin AuIB, inhibits it. Our findings posit a mechanism whereby signaling via alpha3/alpha5/beta4-containing nAChRs promotes lung carcinogenesis.
CHRNA5, ligand-gated ion channel, lung cancer, nicotinic acetylcholine receptor, small cell lung carcinoma
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Copyright © 2013 Improgo, Soll, Tapper and Gardner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI of Published Version
Front Physiol. 2013 Sep 17;4:251. doi: 10.3389/fphys.2013.00251. eCollection 2013. Link to article on publisher's site
Frontiers in physiology
Improgo, Ma. Reina D.; Soll, Lindsey G.; Tapper, Andrew R.; and Gardner, Paul D., "Nicotinic acetylcholine receptors mediate lung cancer growth" (2013). University of Massachusetts Medical School Faculty Publications. 1455.
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This work is licensed under a Creative Commons Attribution 3.0 License.