Open Access

5‑HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability

  • Authors:
    • Yessenia Ballou
    • Alexandria Rivas
    • Andres Belmont
    • Luv Patel
    • Clarissa N. Amaya
    • Shane Lipson
    • Thuraieh Khayou
    • Erin B. Dickerson
    • Zeina Nahleh
    • Brad A. Bryan
  • View Affiliations

  • Published online on: July 19, 2018     https://doi.org/10.3892/mco.2018.1681
  • Pages: 243-254
  • Copyright: © Ballou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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September-2018
Volume 9 Issue 3

Print ISSN: 2049-9450
Online ISSN:2049-9469

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Spandidos Publications style
Ballou Y, Rivas A, Belmont A, Patel L, Amaya CN, Lipson S, Khayou T, Dickerson EB, Nahleh Z, Bryan BA, Bryan BA, et al: 5‑HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability. Mol Clin Oncol 9: 243-254, 2018.
APA
Ballou, Y., Rivas, A., Belmont, A., Patel, L., Amaya, C.N., Lipson, S. ... Bryan, B.A. (2018). 5‑HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability. Molecular and Clinical Oncology, 9, 243-254. https://doi.org/10.3892/mco.2018.1681
MLA
Ballou, Y., Rivas, A., Belmont, A., Patel, L., Amaya, C. N., Lipson, S., Khayou, T., Dickerson, E. B., Nahleh, Z., Bryan, B. A."5‑HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability". Molecular and Clinical Oncology 9.3 (2018): 243-254.
Chicago
Ballou, Y., Rivas, A., Belmont, A., Patel, L., Amaya, C. N., Lipson, S., Khayou, T., Dickerson, E. B., Nahleh, Z., Bryan, B. A."5‑HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability". Molecular and Clinical Oncology 9, no. 3 (2018): 243-254. https://doi.org/10.3892/mco.2018.1681