Abstract
PA28α/β 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 PA28α/β proteins are responsible for breast cancer cell migration, invasion, and metastasis. Knockdown of immunoproteasome core subunit β5i also robustly suppresses the tumor cell migration and invasion. Interestingly, silencing of PA28α/β and β5i 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 PA28α/β represents a potential way for treatment of metastatic breast cancer.
Highlights
Ubiquitin proteasome system (UPS) is critical for protein homeostasis in normal cells [1,2,3]
To identify potential drug targets of breast cancer, in this study we investigate the biological roles of PA28α/β in the proliferation, invasion, and metastasis of breast cancer cells, providing potential strategies for treatment of metastatic breast cancer
Double silencing of PA28α/β significantly suppressed breast cancer cell invasion (Figure 1D)
Summary
Ubiquitin proteasome system (UPS) is critical for protein homeostasis in normal cells [1,2,3]. The 20S immunoproteasome has particular cytokine-inducible subunits β1i, β2i, and β5i that are homolog to β1, β2, and β5 subunits of constitutive proteasome [9,10,11]. These cytokine–inducible subunits facilitate immunoproteasome-generated peptide ligands of MHC class I molecules [12,13,14,15]. Immunoproteasome subunit β5i degrades ATRAP protein and promotes Angiotensin II-induced atrial fibrillation [18]. Kovacsics et al identified that immunoproteasome mediated degradation of heme oxygenase-1 in interferon gamma-stimulated astrocytes contributes to the neurocognitive impairment in HIV-associated neurocognitive disorders [19]
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