Our in vitro and in vivo results paralleled and supported the in silico data, demonstrated that PAK4 induced oncogenic features through the activation of PI3K/AKT pathway in both kinase-dependent and kinase-independent manner, suggesting dual inhibition for PAK4 and PI3K/AKT signaling could be a unique potential therapeutic approach for breast cancer therapy. The gene discussed is AKT1; the disease is breast cancer.