Objective To investigate the effects and mechanism of oncostatin M (OSM)/oncostatin M receptor (OSMR) signaling on the invasive ability of glioblastoma (GBM) cells.

Methods Public single‑cell sequencing datasets were analyzed to clarify the cellular localization of OSM and OSMR in GBM, and verified by immunofluorescence double staining in clinical samples. Transwell invasion assays were performed to evaluate the effects of OSM treatment and OSMR knockdown on the invasive ability of LN229 cells. Transcriptome sequencing combined with bioinformatics analysis was used to screen differentially expressed genes and enrichment pathways. Western blot was applied to verify the activation of the PI3K/Akt pathway and the expression changes of proteins associated with proneural‑mesenchymal transition (PMT).

Results Single‑cell sequencing and immunofluorescence results showed that OSM was mainly expressed in tumor‑associated macrophages, while OSMR was predominantly expressed in GBM cells. OSM treatment significantly enhanced the invasive ability of GBM cells, whereas OSMR knockdown markedly inhibited cell invasion. Transcriptome sequencing and enrichment analysis revealed that differentially expressed genes were significantly enriched in the PI3K/Akt pathway, and Western blot confirmed that OSM/OSMR signaling activated the PI3K/Akt pathway. OSMR knockdown upregulated the expression of the proneural marker OLIG2 and downregulated the expression of the mesenchymal marker CD44, thereby suppressing PMT in GBM cells.

Conclusion OSM/OSMR signaling promotes GBM cell invasion by activating the PI3K/Akt pathway and inducing PMT. This signaling axis is expected to become a potential therapeutic target for GBM.

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