哺乳动物E2F转录因子家族（E2Fs）由8个成员（E2F1-E2F8）组成，分为激活因子（E2F1-E2F3）和抑制因子（E2F4-E2F8），主要调控与细胞增殖、凋亡和分化相关的多个基因的表达，主要以细胞周期为依据。E2F活性通常通过视网膜母细胞瘤蛋白（pRb）、细胞周期蛋白、p53和泛素-蛋白酶途径进行调控。此外，遗传或表观遗传变化导致E2F家族基因表达的失调，改变S期进入和凋亡，这是癌症发生和发展的重要标志。尽管研究表明E2Fs涉及多种人类恶性肿瘤，但E2Fs在口腔癌中的作用机制尚不明确，需要进一步研究。本综述论文着重探讨E2Fs在口腔癌中的作用以及调控E2Fs活性的病因因素，从而转录调控其靶基因的表达，从而促进细胞增殖、转移和药物/治疗耐受性。此外，我们将讨论E2Fs的治疗策略，以预防口腔肿瘤的增长、转移和药物耐受性。 版权所有©2023 Elsevier Ltd.

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.Copyright © 2023. Published by Elsevier Ltd.