FKBP10 may affect the malignant phenotype of oral squamous cell carcinoma cells through the ECM/WNT signaling pathway.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the oral and maxillofacial region with a poor prognosis, and its pathophysiology has not been fully elucidated. Although FKBP10 is overexpressed in multiple malignancies, its function and regulatory mechanism in OSCC remain largely unknown. Methods: OSCC and paired adjacent normal tissue samples were collected, and public datasets including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were integrated. Bioinformatics approaches including Weighted Gene Co-Expression Network Analysis (WGCNA), limma differential expression analysis and machine learning were applied to screen candidate target genes. Single-cell and spatial transcriptome analyses were performed to delineate the main expression domain of FKBP10 and its distribution in macrophages. Cell Counting Kit-8 (CCK-8), colony formation, Transwell, wound healing and flow cytometry assays were conducted to examine the effects of FKBP10 knockdown on the biological behaviors of SCC-9 cells. Western blot and Gene Set Enrichment Analysis (GSEA) were adopted to explore the potential molecular mechanism. Result: Bioinformatics research identified FKBP10 as a significant target gene for OSCC. FKBP10 is predominantly enriched in fibroblasts and significantly upregulated in OSCC tissues. It has a strong positive correlation with M2-type macrophage infiltration and is linked to a negative outcome for patients. FKBP10 knockdown can cause cell apoptosis, stop the cell cycle at the G0/G1 phase, and prevent SCC-9 cells from proliferating, migrating, and invading. Meanwhile, knockdown of FKBP10 downregulated the protein levels of Periostin (POSTN), Integrin Subunit Beta 5 (ITGB5) and key WNT signaling molecules. Conclusion༚FKBP10 may influence the recruitment of M2-type macrophages by regulating the ECM/integrin adhesion signal and the WNT pathway, thereby changing the tumor immune milieu and encouraging the occurrence and progression of OSCC. It is projected to become a promising biomarker and target for prognostic evaluation and targeted therapy of OSCC.