Furthermore, although prior studies have shown that E2F regulates cIAPs, and E2F1 directly promotes MAP3K14 gene expression in osteosarcoma cells25–27, we report for the first time that the E2F transcription factors, E2F4 and E2F5, play a key role in regulating NIK transcription and expression in GBM cells. Here, MAP3K14 is linked to osteosarcoma.