HMGN2 induces pyroptosis in tumour cells by modulating the STT3B/PD‑L1/caspase‑1/GSDMD axis

High‑mobility group nucleosomal‑binding domain 2 (HMGN2) is an abundant conserved protein that acts as a non‑histone nuclear DNA‑binding protein. HMGN2 can be released by activated peripheral blood mononuclear cells, CD8+ T cells and γδ T cells, and can induce tumour cell apoptosis. In the present study, receptors of HMGN2 were detected on tumour cell membranes and the mechanism by which HMGN2 induces tumour cell apoptosis was examined. Flow cytometry was used to determine the degree of HMGN2‑induced apoptosis. To identify notable HMGN2 receptors on tumour cells, the present study used immunoprecipitation and mass spectrometry (IP/MS) to identify protein complexes. Western blotting and immunofluorescence were used to confirm interactions between HMGN2 and oligosaccharyltransferase subunit STT3B (STT3B), and to elucidate the downstream regulatory mechanism of HMGN2. The predictive tools ZDOCK and AlphaFold3 were used to determine the binding conformation of HMGN2 to STT3B. HMGN2 was shown to bind to the membrane and induce the apoptosis of CAL‑27 tumour cells. STT3B was identified via IP/MS as a receptor of HMGN2 on the CAL‑27 membrane and subsequently identified as an important receptor of HMGN2 via an anti‑STT3B blocking assay. ZDOCK and AlphaFold3 analyses revealed that HMGN2 and STT3B formed a stable protein docking model. After incubation with HMGN2, the expression of programmed cell death 1 ligand 1 (PD‑L1)/caspase‑1/gasdermin D (GSDMD) axis components was significantly increased, and PD‑L1 was translocated into the nucleus from the membrane of CAL‑27 cells. The results of the present study indicated that extracellular HMGN2 induced pyroptosis in tumour cells by modulating the STT3B/PD‑L1/caspase‑1/GSDMD axis.