Panoply™ Human CD55 Over-expressing Stable Cell Line

Platinum resistance is a primary cause of poor prognosis in patients with ovarian cancer (OC). Research into targeted therapies addressing drug resistance and the identification of associated biomarkers is crucial for patient treatment. CD55, a cell-surface molecule belonging to the family of complement regulatory proteins, drives chemotherapy resistance and maintains the properties of cancer stem cells (CSCs)-cells closely linked to cancer recurrence and metastasis. In this study, researchers found that CD55 is present in select ovarian cancer tissue samples and the ascites of drug-resistant patients, and is enriched within drug-resistant ovarian cancer cells. Nuclear CD55 undergoes glycosylation and originates from the cell-surface CD55 pool; its nuclear translocation is driven by a transport signal sequence containing the CD55 serine/threonine (S/T) domain. Nuclear CD55 is essential for cisplatin resistance, stemness characteristics, and cell proliferation in ovarian cancer cells. In both in vitro and in vivo models, the CD55 S/T domain is required for nuclear translocation and the induction of cisplatin resistance; deletion of this domain is sufficient to re-sensitize drug-resistant ovarian cancer cells to cisplatin. Within the nucleus, CD55 binds to and inhibits the function of ZMYND8-an epigenetic regulator and tumor suppressor-coinciding with elevated levels of H3K27 trimethylation and components of the Polycomb Repressive Complex 2 (PRC2).

Researchers examined H3K27Me3 levels in CD55-knockout (KO) and CD55-overexpressing CP70 cells, finding that CD55 increased H3K27Me3 levels in the nuclear fraction (Figure 1A). Given that ZMYND8 and CD55 exert opposing effects on H3K27Me3, the researchers investigated whether CD55 induces the expression of PRC2-associated proteins (EZH2, SUZ12, EED, JARID2, EZH1, and AEBP2). CD55 overexpression led to elevated protein expression levels of EZH2, SUZ12, EED, JARID2, and AEBP2 in both whole-cell lysates and nuclear fractions (Figure 1B). The finding that CD55 positively regulates PRC2 target genes was further confirmed by bulk RNA-seq data (Figures 7C and D). Next, the researchers investigated whether CD55 forms a complex with PRC2 components. Co-immunoprecipitation (Co-IP) and subsequent immunoblotting in CD55-overexpressing (OE) cells revealed that ZMYND8 formed a complex with EZH2, SUZ12, and CD55 (Figure 1E). Subsequent Co-IP and immunoblotting using an anti-SUZ12 antibody demonstrated interactions with CD55 and EZH2 (Figure 1F). Similarly, immunoprecipitation of EZH2 showed interactions with CD55 and SUZ12 (Figure 1G). These results indicate that in platinum-resistant ovarian cancer cells, CD55 forms a nuclear complex with ZMYND8 and the PRC2 components SUZ12 and EZH2 (Figure 1H).

Figure 1. Nuclear CD55 associates with PRC2 members and regulates H3K27me3 mark. (Bharti R, et al., 2024)