It has been reported that NF-κB could mediate the secretion of proinflammatory cytokines (IL-6 and IL-8) in various types of cancer.49 More recently, a study showed that IL-6 could induce highly oncogenic, drug-resistant, stem-like phenotype in cancer cells.50 Our data herein elucidated a novel PAK1/NF-κB/IL-6 signaling pathway that might be partly responsible for the transformation of a stem-like phenotype in RCC cells. Here, PAK1 is linked to renal cell carcinoma.