In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 7 ( 2023-7-25), p. e0289098-
Abstract:
Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect of α7 nAChR on cell proliferation was abolished by application of Gαi/o and Gαq protein blockers. Specifically, application of the Gαi/o inhibitor pertussis toxin was found to abolish choline-mediated cell proliferation and intracellular calcium transient response. These findings were corroborated by expression of a G protein binding dominant negative nAChR subunit (α7 345-348A ), which resulted in significantly attenuating calcium signaling and cellular proliferation in response to choline. Our study shows a new role for G protein signaling in the mechanism of α7 nAChR-associated breast cancer growth.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0289098
DOI:
10.1371/journal.pone.0289098.g001
DOI:
10.1371/journal.pone.0289098.g002
DOI:
10.1371/journal.pone.0289098.g003
DOI:
10.1371/journal.pone.0289098.g004
DOI:
10.1371/journal.pone.0289098.g005
DOI:
10.1371/journal.pone.0289098.g006
DOI:
10.1371/journal.pone.0289098.g007
DOI:
10.1371/journal.pone.0289098.s001
DOI:
10.1371/journal.pone.0289098.s002
DOI:
10.1371/journal.pone.0289098.r001
DOI:
10.1371/journal.pone.0289098.r002
DOI:
10.1371/journal.pone.0289098.r003
DOI:
10.1371/journal.pone.0289098.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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