S100A13 transcriptionally activated by SP1 facilitates osteosarcoma metastasis

BACKGROUND: Osteosarcoma is a highly aggressive primary bone malignancy in which distant metastasis critically determines patient prognosis. However, the molecular drivers of metastasis remain incompletely understood, making the elucidation of these drivers a research priority. METHODS: We integrated single-cell and bulk RNA sequencing data to identify cell populations associated with metastasis and to screen for candidate therapeutic targets. Bioinformatics tools predicted upstream transcriptional regulators. Functional roles and transcriptional regulation were assessed via wound-healing, Transwell, and luciferase reporter assays. RESULTS: Single-cell analysis of osteosarcoma heterogeneity identified the osteoblastic subcluster C2_OB as a major contributor to metastasis. cNMF analysis defined a metastasis-associated expression program (module 2) highly active in C2_OB, within which S100A13 emerged as a novel signature gene. S100A13 was overexpressed in osteosarcoma and correlated with metastasis and poor prognosis. Functional assays demonstrated that S100A13 promoted cell migration and invasion. Mechanistically, the transcription factor SP1 directly binds to the S100A13 promoter, activates its transcription, and thereby enhances the metastatic capacity of osteosarcoma cells. CONCLUSION: This study identifies S100A13 as a biomarker for osteosarcoma metastasis and poor prognosis, and delineates an SP1/S100A13 axis that drives metastatic progression.