Date Available
8-10-2025
Year of Publication
2023
Degree Name
Doctor of Philosophy (PhD)
Document Type
Doctoral Dissertation
College
Medicine
Department/School/Program
Toxicology and Cancer Biology
First Advisor
Dr. Qiou Wei
Abstract
Small cell lung cancer (SCLC), which accounts for 10-15% of all lung cancer, is the most malignant type that tends to grow fast and spread in its early stages. The 5-year survival rate remains low at 6% overall. Thus, new therapeutic methods and pharmacological targets for SCLC patients are urgently needed. We present novel data indicating that the synthesis of serotonin is upregulated in SCLC compared to normal bronchial epithelial cells and non-small cell lung cancer. Serotonin signaling plays a critical role in various physiological and pathological processes. However, its contribution to SCLC development has not been well understood. The goal of this study is to investigate the role of serotonin signaling in human SCLC development and to test the hypothesis that disrupting the serotonin axis inhibits cancer growth in vitro and in vivo. Here we demonstrated that elevated serotonin contributes to SCLC development, whereas blocking serotonin receptor, HTR3A, prevents part of the serotonin mitogenic effect. Additionally, inhibition of serotonin synthesis enzyme, TPH1, effectively reduces cell proliferation, induces cell apoptosis, as well as suppresses metastasis in vitro and in vivo. We also reported the SCLC organoids from xenograft tumor and liver metastasis tissue, as well as represented the value of interruption TPH1-serotonin-HTR3A axis in both tumoriods.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2023.397
Recommended Citation
Hao, Yanning, "UNDERSTANDING AND TARGETING THE TPH1-SEROTONIN-HTR3A AXIS IN SMALL CELL LUNG CANCER" (2023). Theses and Dissertations--Toxicology and Cancer Biology. 47.
https://uknowledge.uky.edu/toxicology_etds/47
