DDOST mediates cervical cancer cell malignant progression by interacting with SMARCA4

DDOST is generally recognized as a regulator of glycosylation homeostasis and its deficiency can cause congenital glycosylation disorders. However, its role in tumors has not yet been elucidated. This study aimed to explore the functional role of DDOST and its related mechanisms in cervical cancer (CC). The clinical correlation of DDOST was analyzed using The Cancer Genome Atlas (TCGA) database and verified by immunohistochemistry slides of clinical samples. Cell growth, proliferation, apoptosis, migration, and invasion were evaluated. Co-immunoprecipitation (co-IP) and liquid chromatography with tandem mass spectrometry (LC-MS) were used to identify interacting proteins. The functions of the interacting proteins were further confirmed using genetic rescue experiments. A subcutaneous xenograft model was used to investigate tumorigenesis. Based on the TCGA data and our collected clinical samples, we found that DDOST was associated with a more aggressive pathological phenotype. DDOST also promoted several malignant phenotypes in CC cells. Co-IP coupled with LC-MS identified the interacting protein SMARCA4, and western blotting confirmed a positive interaction between these two proteins. Similar to in vivo tumorigenesis, cell growth and migration were markedly rescued by SMARCA4 overexpression after DDOST knockdown, as was tumorigenesis in vivo. This study showed that DDOST promoted tumorigenesis in CC and was identified it as a possible novel biomarker or therapeutic target in CC. The interaction between DDOST and SMARCA4 is a potential mechanism that requires further investigation.