PAK5 Promotes RNA Helicase DDX5 Sumoylation and miRNA-10b Processing Via Kinase-Dependent Manner in Breast Cancer

P21-activated kinase 5 (PAK5) plays an important role in tumors. Yet, the potential functional role of PAK5 during mammary tumorigenesis in vivo is unknown. Here, we showed that PAK5 deficiency repressed MMTV-PyVT-driven breast tumorigenesis. DEAD-box RNA helicase 5 (DDX5) was a new substrate of PAK5, which was phosphorylated on threonine 69. PAK5-mediated DDX5 phosphorylation promoted breast cancer cell proliferation and metastasis in vitro and in vivo. The increased expression levels of PAK5 and DDX5 were associated with metastasis and poor outcomes of breast cancer patients. PAK5 facilitated the phosphorylation-dependent sumoylation of DDX5 to stabilize DDX5. Both the phosphorylation and sumoylation of DDX5 enhanced the formation of DDX5/Drosha/DGCR8 complex, thus promoting the miR-10b processing. Finally, we verified decreased expression of DDX5 phosphorylation and sumoylation and mature miR-10b in PAK5−/−/MMTV-PyVT transgenic mice. Our findings provide insights into the function of PAK5 in miRNA biogenesis, which might be a potential therapeutic target for breast cancer.