Serotonin transporter acts as a tumor suppressor in cervical cancer

Although neuromodulation has emerged as a critical factor in cancer biology, its involvement in cervical cancer remains largely unexplored. In this study, we identified the serotonin transporter (SERT), a marker of serotonergic neurons, as a potential tumor suppressor in cervical cancer. SERT expression was progressively reduced with increasing severity of cervical lesions and was negatively associated with patient survival. Functionally, SERT overexpression significantly inhibited cervical cancer cell viability and xenograft tumor growth in the presence of serotonin (5-Hydroxytryptamine, 5-HT), both in vitro and in vivo. Mechanistically, SERT promoted mitochondrial-mediated tumor cell apoptosis through upregulation of Bax and cleaved caspase-3, without affecting cell proliferation. This proapoptotic effect may be associated with inhibition of STAT3 pathway activation. Notably, these tumor-suppressive effects could be largely abolished by fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) widely used as a first-line antidepressant. Collectively, our findings reveal a direct suppressive function of the SERT-5-HT axis in cervical cancer cells and suggest a potential risk that FLX may interfere with this antitumor activity, warranting further investigation to assess its impact on cervical cancer progression.