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5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability
Symptoms of depression are present in over half of all cancer patients, and selective serotonin reuptake inhibitor (SSRI) anti-depressant medications are prescribed to nearly a quarter of these individuals in order to cope with their disease. Previous studies have provided evidence that elevated ser...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109681/ https://www.ncbi.nlm.nih.gov/pubmed/30155245 http://dx.doi.org/10.3892/mco.2018.1681 |
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author | Ballou, Yessenia Rivas, Alexandria Belmont, Andres Patel, Luv Amaya, Clarissa N. Lipson, Shane Khayou, Thuraieh Dickerson, Erin B. Nahleh, Zeina Bryan, Brad A. |
author_facet | Ballou, Yessenia Rivas, Alexandria Belmont, Andres Patel, Luv Amaya, Clarissa N. Lipson, Shane Khayou, Thuraieh Dickerson, Erin B. Nahleh, Zeina Bryan, Brad A. |
author_sort | Ballou, Yessenia |
collection | PubMed |
description | Symptoms of depression are present in over half of all cancer patients, and selective serotonin reuptake inhibitor (SSRI) anti-depressant medications are prescribed to nearly a quarter of these individuals in order to cope with their disease. Previous studies have provided evidence that elevated serotonin (5-HT) and serotonin receptor levels may contribute to oncogenic progression, yet little is known regarding the mechanism by which this occurs. The data demonstrated that serotonin receptor mRNAs and proteins are expressed across diverse cancer types, and that serotonin stimulation of tumor cells activates oncogenic signaling mediators including components of the AKT, CREB, GSK3, and MAPK pathways. Selective pharmacological inhibition of the seven known classes of 5-HT receptors in sarcoma and breast cancer cells resulted in dose dependent decreases in tumor cell viability, activation of the p53 DNA damage pathway, suppression of MAPK activity, and significantly reduced tumor volume in an in ovo model. Based on a retrospective clinical analysis of 419 patients diagnosed with breast cancer, we discovered that use of SSRIs was associated with a 2.3-fold increase in tumor proliferation rates for late stage patients based on their Ki-67 index (P=0.03). These data provide evidence that serotonin signaling pathways, which treating oncologists often pharmacologically target to assist cancer patients to psychologically cope with their illness, activate signaling pathways known to promote tumor growth and survival. |
format | Online Article Text |
id | pubmed-6109681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-61096812018-08-28 5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability Ballou, Yessenia Rivas, Alexandria Belmont, Andres Patel, Luv Amaya, Clarissa N. Lipson, Shane Khayou, Thuraieh Dickerson, Erin B. Nahleh, Zeina Bryan, Brad A. Mol Clin Oncol Articles Symptoms of depression are present in over half of all cancer patients, and selective serotonin reuptake inhibitor (SSRI) anti-depressant medications are prescribed to nearly a quarter of these individuals in order to cope with their disease. Previous studies have provided evidence that elevated serotonin (5-HT) and serotonin receptor levels may contribute to oncogenic progression, yet little is known regarding the mechanism by which this occurs. The data demonstrated that serotonin receptor mRNAs and proteins are expressed across diverse cancer types, and that serotonin stimulation of tumor cells activates oncogenic signaling mediators including components of the AKT, CREB, GSK3, and MAPK pathways. Selective pharmacological inhibition of the seven known classes of 5-HT receptors in sarcoma and breast cancer cells resulted in dose dependent decreases in tumor cell viability, activation of the p53 DNA damage pathway, suppression of MAPK activity, and significantly reduced tumor volume in an in ovo model. Based on a retrospective clinical analysis of 419 patients diagnosed with breast cancer, we discovered that use of SSRIs was associated with a 2.3-fold increase in tumor proliferation rates for late stage patients based on their Ki-67 index (P=0.03). These data provide evidence that serotonin signaling pathways, which treating oncologists often pharmacologically target to assist cancer patients to psychologically cope with their illness, activate signaling pathways known to promote tumor growth and survival. D.A. Spandidos 2018-09 2018-07-19 /pmc/articles/PMC6109681/ /pubmed/30155245 http://dx.doi.org/10.3892/mco.2018.1681 Text en Copyright: © Ballou et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Ballou, Yessenia Rivas, Alexandria Belmont, Andres Patel, Luv Amaya, Clarissa N. Lipson, Shane Khayou, Thuraieh Dickerson, Erin B. Nahleh, Zeina Bryan, Brad A. 5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability |
title | 5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability |
title_full | 5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability |
title_fullStr | 5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability |
title_full_unstemmed | 5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability |
title_short | 5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability |
title_sort | 5-ht serotonin receptors modulate mitogenic signaling and impact tumor cell viability |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109681/ https://www.ncbi.nlm.nih.gov/pubmed/30155245 http://dx.doi.org/10.3892/mco.2018.1681 |
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