2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.03D.01 Mechanistic Study of 5-Hydroxytryptamine-Mediated Promotion of Non-Small Cell Lung Cancer Metastasis by Regulation of RPL24

EP.03D.01 Mechanistic Study of 5-Hydroxytryptamine-Mediated Promotion of Non-Small Cell Lung Cancer Metastasis by Regulation of RPL24

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The study, led by Yan Sun and colleagues from the Department of Oncology at The Second Hospital of Dalian Medical University, investigates the role of 5-hydroxytryptamine (5-HT) in promoting non-small cell lung cancer (NSCLC) metastasis through the regulation of the ribosomal protein RPL24. NSCLC is a prevalent and aggressive form of lung cancer, comprising 80-85% of cases. The study focuses on the gut-lung axis, highlighting 5-HT's significance, which is mainly produced in the gastrointestinal tract and influenced by gut microbiota.<br /><br />Methods involved measuring 5-HT levels in NSCLC patients' blood, performing metagenomic analyses of gut microbiota, and identifying differentially expressed genes in NSCLC cells treated with 5-HT. The researchers employed gene silencing and overexpression techniques to explore RPL24's role in cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT).<br /><br />Key findings include:<br />1. Elevated 5-HT levels were associated with distant metastases in NSCLC patients, suggesting a potential biomarker for metastasis.<br />2. Patients with metastases exhibited diverse gut microbiota, with Clostridium difficile abundance linked to higher 5-HT levels.<br />3. RPL24 was identified as a crucial molecule in 5-HT-mediated cancer progression. Silencing RPL24 enhanced migration and EMT in cancer cells, whereas its overexpression reduced these effects.<br />4. The 5-HT receptor HT3A was more expressed in NSCLC tissues. Ondansetron, an HT3A receptor antagonist, partially reversed the pro-migratory and invasive effects of 5-HT, implicating HT3A in the regulatory pathway of RPL24.<br /><br />The study concludes that 5-HT increases NSCLC metastasis by downregulating RPL24 via HT3A, enhancing cell migration and invasion through EMT pathways. These insights might contribute to developing targeted therapies for NSCLC metastasis.

Asset Subtitle

Yan Sun

Meta Tag

Speaker Yan Sun

Topic Tumor Biology – Translational Biology

Keywords

5-hydroxytryptamine

non-small cell lung cancer

NSCLC metastasis

ribosomal protein RPL24

gut-lung axis

gut microbiota

epithelial-mesenchymal transition

HT3A receptor

Ondansetron

targeted therapies