Role of E2F transcription factor in oral cancer: Recent insight and advancements

The family of mammalian E2F transcription factors (E2Fs) comprise of 8 members (E2F1-E2F8) classified as activators (E2F1-E2F3) and repressors (E2F4-E2F8) primarily regulating the expression of several genes related to cell proliferation, apoptosis and differentiation, mainly in a cell cycle-dependent manner. E2F activity is frequently controlled via the retinoblastoma protein (pRb), cyclins, p53 and the ubiquitin-proteasome pathway. Additionally, genetic or epigenetic changes result in the deregulation of E2F family genes expression altering S phase entry and apoptosis, an important hallmark for the onset and development of cancer. Although studies reveal E2Fs to be involved in several human malignancies, the mechanisms underlying the role of E2Fs in oral cancer lies nascent and needs further investigations. This review focuses on the role of E2Fs in oral cancer and the etiological factors regulating E2Fs activity, which in turn transcriptionally control the expression of their target genes, thus contributing to cell proliferation, metastasis, and drug/therapy resistance. Further, we will discuss therapeutic strategies for E2Fs, which may prevent oral tumor growth, metastasis, and drug resistance.