In summary, as shown in genetic regulatory network depicted in Fig. 7f, we described a novel mechanism by which interaction of SOX2 and KLF4, as the transcription co-activators, significantly upregulated PIK3CA expression, thereby activating the PI3K/AKT signaling pathway, and ultimately enhanced nasopharyngeal carcinoma tumorigenesis. This evidence concerns the gene KLF4 and nasopharyngeal carcinoma.