Abstract
Pard3 is a core component of the Par complex and is a critical regulator of cell polarity. However, the biological role of Pard3 in breast cancer (BC) remains unclear. In this study we found that Pard3 levels were down-regulated in BC cells and tissues. Pard3 down-regulation was associated with the TNM stage of BC. Further, Pard3 knockdown enhanced colony formation and metastasis in vitro and in vivo. Interestingly, Pard3 knockdown also enhanced Snail1 deubiquitination and promoted BC invasion and migration via Snail1. Moreover, Pard3 silencing led to activation of the NFκB pathway, promoting the expression of USP28. Subsequently, USP28 interacted with and deubiquitinated Snail1; these effects were dependent on GSK-3β-mediated phosphorylation. Together, the findings indicated that Pard3 knockdown facilitated the migration and invasion of BC cells by enhancing USP28-mediated Snail1 deubiquitination. Collectively, targeting the Pard3/NFκB/USP28/Snail1 signaling pathway might be a promising treatment option for breast cancer.