Abstract
Breast cancer is the second leading cause of cancer-related death among women worldwide. Emerging evidence suggests that chromobox homolog 2 (CBX2) is overexpressed in breast cancer and plays an essential role in tumor progression. However, its expression and functional roles in breast cancer development and progression require further exploration. Here, we evaluated CBX2 expression in breast cancer using mRNA expression data from the TCGA database; CBX2 expression was upregulated in breast cancer. Furthermore, upregulated CBX2 expression was significantly associated with poorer overall survival (OS) and progression-free survival (PFS) of breast cancer patients. Immunohistochemical analysis of CBX2 expression in a tissue microarray (TMA) cohort yielded concordant results. Univariate and multivariate analyses showed that elevated CBX2 expression was significantly and independently associated with poorer OS of patients in this TMA cohort. Additionally, we performed in vitro functional assays to evaluate the proliferation, migration, and invasion abilities of breast cancer cell lines wherein CBX2 was knocked down using short hairpin RNA (shRNA). CBX2 silencing inhibited cell proliferation, migration, and invasion in vitro. Furthermore, knockdown of CBX2 markedly reduced breast tumorigenesis in xenograft mouse models. Functional and pathway enrichment analyses indicated a positive correlation between high CBX2 expression and activation of the PI3K/AKT pathway, which were further confirmed by western blot and immunohistochemical analyses of mouse tumors. Our findings indicate that CBX2 is a potential prognostic biomarker and therapeutic target for breast cancer.