RAN-S100A10-EGFR axis facilitates papillary thyroid cancer metastasis by PI3K/AKT signaling.

[BACKGROUND] The incidence of thyroid cancer has been increasing in recent years, with papillary thyroid carcinoma (PTC) accounting for the majority of cases. Accumulating studies have demonstrated that S100A10 acts as an oncogene in the progression of various malignancies. However, the function and specific mechanisms of S100A10 in thyroid cancer remain poorly defined.

[METHODS] Single-cell RNA sequencing data of PTC from public databases were analyzed to screen differentially expressed genes (DEGs), among which S100A10 emerged as a potential biomarker associated with PTC metastasis and prognosis. The expression of S100A10 in tissues and cell lines were validated by RT-qPCR and western blot. Protein-protein interactions were confirmed using mass spectrometry analysis and co-immunoprecipitation. The subcellular localization of the protein was determined by immunofluorescence. Stable PTC cell lines overexpressing S100A10 were constructed and followed by transwell assays, wound-healing assays, and western blot for EMT capability detection.

[RESULTS] S100A10 was found to play essential roles in tumor metastasis and was associated with unfavorable prognosis in patients with PTC. S100A10 was expressed higher in both PTC tissues and cells. Furthermore, both in vitro and in vivo experiments confirmed that S100A10 activates the PI3K/AKT signaling and promotes EMT in PTC cells, enhancing the invasive capabilities of tumors. S100A10 could interact with both RAN and EGFR intracellularly, forming a RAN-S100A10-EGFR regulatory axis. Finally, several potential drugs targeting S100A10 were identified for further in-depth research.

[CONCLUSION] These findings clarify the role of S100A10 and RAN in PTC progression and highlight their potential as therapeutic targets, linking EMT with PI3K/AKT signaling.