The oncogenic role of SPOCK1 in lung carcinoma by promoting immune evasion and its related mechanisms.

UNLABELLED

The progression of cancer is remarkable for its ability to evade the immune system. SPOCK1 plays crucial roles in lung carcinoma malignant phenotypes and CD8 + T cell infiltration. Here, we looked at how SPOCK1 drives immune evasion in lung cancer and unraveled the underlying mechanisms. Expression analyses were performed using quantitative PCR (qPCR), immunoblotting, or immunohistochemistry (IHC). Cell proliferation and viability were assessed by MTT assay. Cell apoptosis, invasion, and sphere formation were evaluated. The POU2F1-SPOCK1 relationship was analyzed by luciferase and ChIP assays. The ELAVL1-SPOCK1 relationship was verified by SPOCK1 mRNA stability analysis. In vivo validation of the POU2F1-SPOCK1 axis was performed using xenograft assays along with lentiviral rescue approach. Increased levels of SPOCK1 predicted poor clinical outcomes in lung carcinoma patients (n = 39) and were associated with PDL1 expression and the tumor mutational burden (TMB). SPOCK1 depletion suppressed the growth, invasion, and stemness of lung cancer cells. Moreover, SPOCK1 depletion increased TNF-α and IFN-γ secretion, enhanced CD8 + T cell viability, and suppressed CD8 + T cell apoptosis in vitro. Mechanistically, POU2F1 transcriptionally controlled SPOCK1 expression. SPOCK1 restoration reversed the impact of POU2F1 depletion on cancer cell malignant phenotypes and tumor immune evasion. Furthermore, ELAVL1 increased SPOCK1 mRNA stability to upregulate SPOCK1. Additionally, SPOCK1 increase rescued the growth of POU2F1-depleted A549 xenografts in vivo (n = 5 per group). Our findings demonstrate that SPOCK1 upregulation induced by POU2F1 or ELAVL1 contributes to lung carcinoma progression by sustaining cancer cell malignant phenotypes and promoting immune evasion, suggesting SPOCK1 as a potential target for lung cancer therapy.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s10616-025-00804-9.