PA28α/β Promote Breast Cancer Cell Invasion and Metastasis via Down-Regulation of CDK15

PA28 alpha/beta activated immunoproteasome frequently participates in MHC class I antigen processing, however, whether it is involved in breast tumor progression remains largely unclear. Here, our evidences show that PA28 alpha/beta proteins are responsible for breast cancer cell migration, invasion, and metastasis. Knockdown of immunoproteasome core subunit beta 5i also robustly suppresses the tumor cell migration and invasion. Interestingly, silencing of PA28 alpha/beta and beta 5i up-regulates the protein expression of cyclin-dependent kinase 15 (CDK15). Our data further indicate that the loss of CDK15 is important for breast tumor cell invasion and metastasis. Taken together, this study implicates that targeting of PA28 alpha/beta represents a potential way for treatment of metastatic breast cancer.