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Serotonin promotes aggressive features in breast cancer cells by modulating proliferation and migration, hormone receptors and HER2 expression.

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Molecular and cellular endocrinology 📖 저널 OA 4.8% 2022: 0/3 OA 2023: 0/3 OA 2024: 0/3 OA 2025: 0/2 OA 2026: 1/8 OA 2022~2026 2026 Vol.612() p. 112692
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Paixão LP, Nascimento Junior JXD, Espírito Santo MESFD, Imbroisi Filho R, Bernardo Leandro JG, Mundim D

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Serotonin (5-HT), a key regulator of epithelial homeostasis, plays a paradoxical role in breast cancer progression.

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APA Paixão LP, Nascimento Junior JXD, et al. (2026). Serotonin promotes aggressive features in breast cancer cells by modulating proliferation and migration, hormone receptors and HER2 expression.. Molecular and cellular endocrinology, 612, 112692. https://doi.org/10.1016/j.mce.2025.112692
MLA Paixão LP, et al.. "Serotonin promotes aggressive features in breast cancer cells by modulating proliferation and migration, hormone receptors and HER2 expression.." Molecular and cellular endocrinology, vol. 612, 2026, pp. 112692.
PMID 41177387 ↗

Abstract

Serotonin (5-HT), a key regulator of epithelial homeostasis, plays a paradoxical role in breast cancer progression. This study investigates the impact of 5-HT signaling on hormone receptor expression, cell proliferation, therapeutic response, and tumor aggressiveness in breast cancer cells. We demonstrate that 5-HT activates transcriptional factors in MCF-7 cells, collectively enhancing cancer hallmarks such as sustained proliferation and invasiveness. Notably, 5-HT downregulates mRNA expression of estrogen receptor (ER), progesterone receptor (PR), and HER2, inducing a phenotype reminiscent of triple-negative breast cancer. Despite these phenotypic changes, acute 5-HT treatment does not impair the effectiveness of tamoxifen in vitro. In vivo, administration of fluoxetine, a selective serotonin reuptake inhibitor, accelerates tumor growth and increases malignancy in a murine model. These findings underscore the ability of 5-HT to reprogram hormone receptors expression profiles and to promote a more aggressive cancer phenotype.

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