The lysosome-associated SLAMF7 inhibits the development of ovarian cancer by promoting lysosomal damage

Ovarian cancer (OC) is currently the 5th cancer-related death in the United States (Torre et al., 2018; Armstrong et al., 2022). Globally, approximately 140,000 women die from OC annually (Penny, 2020). One of the major challenges in treating OC is that most patients already experience disease progression at the time of initial diagnosis (Armstrong et al., 2021). In addition, owing to late diagnosis and high metastatic potential, OC has a high mortality rate, necessitating new treatment strategies to improve outcomes (Ferraresi et al., 2020). Lysosome-associated membrane protein 3 is highly expressed in epithelial OC and is significantly related to poor survival outcomes in epithelial OC patients (Wang et al., 2017). β-Glucocerebrosidase, encoded by GBA, is a lysosomal enzyme that inhibits AXL signaling and represents a promising target for overcoming platinum resistance in OC (Wang et al., 2023a). The role of lysosomal function-related pathways in OC requires further exploration and may help in the development of new treatment strategies.

Lysosomes are signaling hubs and degradation centers of cells and are involved in cellular development, aging, and homeostasis (Yang and Wang, 2021). Lysosomal membrane permeabilization (LMP) is a typical phenomenon associated with lysosomal changes, leading to the leakage of lysosomal contents (Hu et al., 2021). LMP and soluble lysosomal contents, including proteases from the cathepsin family, are released into the cytoplasm, promoting a regulated cell death process such as lysosome-dependent cell death (LDCD) (Serrano-Puebla and Boya, 2018). Lysosomes have emerged as therapeutic targets in human diseases (Wang et al., 2018). Therefore, seeking treatment strategies that disrupt lysosomal stability or enhance, restore, or maintain lysosomal function may improve the prognosis of OC.

The evaluation of sensitive/resistant target treatments for subgroups based on tumor biomarker profiling may enhance the predictive value of immune therapy responses in OC (Morand et al., 2021). The recurrence-associated molecular biomarker SLAMF7 can be used for the early identification of high recurrence risk and poor prognosis in patients with OC (Zhang et al., 2020). SLAMF7 is a key immune infiltration-related gene in patients with OC (Su et al., 2021). SLAMF7 is also a prognostic gene associated with immune-activated cell death in OC patients (Zhang et al., 2022). As a DNA methylation-related prognostic gene, SLAMF7 could be applied to assess the differences in immune characteristics in OC patients, which may help improve immune therapy in OC patients (Wang et al., 2023b). Therefore, SLAMF7 may be a potential biomarker for monitoring prognosis in OC; however, whether it can be utilized as an adjunct target for chemotherapy remains unknown.

Therefore, this study focused on analyzing the prognostic value of lysosome-associated genes in OC patients. We also validated the role of Lysosome-related SLAMF7 in the malignant characterization of OC cells and tumorigenesis in nude mice, in order to provide new theoretical basis for the development of OC treatment methods.

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