Background: Metastasis is a major obstacle in the treatment of cervical cancer (CC), and SPOP-mediated regulatory effects are involved in metastasis. However, the mechanisms have not been fully elucidated. Methods: Proteomic sequencing and SPOP immunohistochemistry (IHC) were performed for the pelvic lymph node (pLN)-positive and non-pLN groups of CC patients. The corresponding patients were stratified by SPOP expression level for overall survival (OS) and relapse-free survival (RFS) analysis. In vitro and in vivo tests were conducted to verify the causal relationship between SPOP expression and CC metastasis. Multiplex immunofluorescence (m-IF) and the HALO system were used to analyse the mechanism, which was further verified by in vitro experiments. Results: SPOP is upregulated in CC with pLN metastasis and negatively associated with patient outcome. In vitro and in vivo, SPOP promotes CC proliferation and metastasis. According to m-IF and HALO analysis, SPOP may promote CC metastasis by promoting the separation of PD-1 from PD-L1. Finally, it was further verified that SPOP can achieve immune tolerance by promoting the movement of PD-1 away from PD-L1 in spatial location and function. Conclusion: This study shows that SPOP can inhibit the immune microenvironment by promoting the movement of PD-1 away from PD-L1, thereby promoting pLN metastasis of CC and resulting in worse OS and RFS.
CITATION STYLE
Wu, J., Wu, Y., Guo, Q., chen, S., Wang, S., Wu, X., … Ju, X. (2022). SPOP promotes cervical cancer progression by inducing the movement of PD-1 away from PD-L1 in spatial localization. Journal of Translational Medicine, 20(1). https://doi.org/10.1186/s12967-022-03574-6
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