OTUB1/SLC7A11 axis promoted AKT signaling activation to mediate ovarian cancer progression

OTUB1 functions as a deubiquitinating enzyme (DUB) and has been reported to be associated with tumor progression. This study aimed to investigate the role of OTUB1 signaling in ovarian cancer progression.

Twenty-five patients diagnosed with ovarian cancer were enrolled and divided into groups based on tumor stage (high/low) and the presence or absence of lymphatic metastasis to analyze OTUB1 expression via Immunohistochemical (IHC) staining. Data from 578 ovarian cancer patients sourced from The Cancer Genome Atlas (TCGA) were downloaded for survival analysis. Cell proliferation and migration were evaluated using CCK8 and Transwell assays. Western blotting and immunostaining were performed to assess the activation of the OTUB1/SLC7A11/AKT signaling pathway.

Our study found that OTUB1 expression was upregulated in ovarian cancer tissues and that higher expression was associated with poor prognosis, and more intriguingly, high-stage and lymph node metastasis ovarian cancer samples exhibited significantly elevated expression of OTUB1.Through in vitro experimental validation, OTUB1 overexpression in ovarian cancer cells promoted the increased cell proliferation, migration, and colony formation. Moreover, OTUB1 led to the upregulation of SOX2 expression, which was implicated with cancer cell stemness. Mechanistically, we further identified that OTUB1 could upregulate SLC7A11 expression, which subsequently activated the PI3K/AKT signaling pathway to promote ovarian cancer progression.

This study highlights the pro-tumor role of OTUB1/SLC7A11 in ovarian cancer through the activation of the PI3K/AKT signaling pathway, offering new insights into potential targeted therapies for ovarian cancer.