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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 (α7345-348A), 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.


This article was originally published in PLoS ONE, volume 18, issue 7, in 2023.

journal.pone.0289098.s001.tiff (453 kB)
S1 Fig. Cell surface labeling of nAChRs using BTX. MCF-7 cells were labeled with 100 nM BTX. Cell membranes were not permeabilized in these labeling experiments. Bottom panel shows a representative image of a labeled cell. Scale bar = 5μm. (TIFF)


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This work is licensed under a Creative Commons Attribution 4.0 License.



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