Moreover, extracellular and intracellular stimuli pass through the TGF-β signaling pathway to E2F4, thereby influencing the cellular process through transcriptional regulation of its target genes NEK2 and PANK1. Uncontrolled NEK2 activity has been reported to activate several oncogenic pathways, thereby inducing cancer cell proliferation and metastasis [45]. Here, E2F4 is linked to cancer.