PAK5 Induces EMT and Promotes Cell Migration and Invasion byActivating the PI3K/AKT Pathway in Ovarian Cancer

Ovarian cancer is the most lethal gynecologic cancer and currently ranksfifth in causing cancer-related deaths among women.P21cdc42/rac1-activated kinase 5 (PAK5) is a newly identified protein that has been indicated to have oncogenic potential. Thepresent study investigated the expression level of PAK5 in clinical ovarian cancer and the functional roles of PAK5 in ovariancancer progression. It was initially found that PAK5 was highly expressed in ovarian cancer tissues, particularly in patients withdistant metastasis. Higher expression of PAK5 predicted poor survival fates in patients with ovarian cancer (p=0008).Knockdown of PAK5 in SKOV3 cells caused epithelial cell phenotypes, whereas overexpression of PAK5 led to remarkablemesenchymal cell phenotypes in A2780 cells. When PAK5 was depleted from SKOV3 cells, cells exhibited impaired woundrecovery abilities. Cell migration and invasion abilities were also significantly inhibited. On the contrary, when PAK5 wasoverexpressed in A2780 cells, the wound recovery ability was enhanced by 68%. Cell migration and invasion abilities wereconsistently increased to approximately 2-fold. After knockdown of PAK5, the phosphorylation levels of PI3K p85 atTyr458 and its downstream AKT at Ser473 were both decreased. The total protein of PI3K and AKT as well as thephosphorylation level of AKT at Thr308 remained unaffected. These data suggested that PI3K induced epithelial-to-mesenchymal transition and promoted cell migration and invasion by activating the PI3K/AKT pathway in ovarian cancer. Theoncogenic potential of PAK5 in ovarian cancer might suggest that any therapeutic strategies targeting PAK5 had the promisingvalue for ovarian cancer treatment.