School of Health and Wellbeing, Faculty of Health, Engineering and Sciences, The University of Southern Queensland, Toowoomba, Australia.
School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
Rev Med Virol. 2015 Nov;25(6):345-53. doi: 10.1002/rmv.1834. Epub 2015 Mar 17.
Fanconi anemia (FA) is a rare recessive disorder associated with chromosomal fragility. FA patients are at very high risk of cancers, especially head and neck squamous cell carcinomas and squamous cell carcinomas caused by infection of human papillomaviruses (HPVs). By integrating into the host genome, HPV oncogenes E6 and E7 drive the genomic instability to promote DNA damage and gene mutations necessary for carcinogenesis in FA patients. Furthermore, E6 and E7 oncoproteins not only inhibit p53 and retinoblastoma but also impair the FANC/BRCA signaling pathway to prevent DNA damage repair and alter multiple signals including cell-cycle checkpoints, telomere function, cell proliferation, and interference of the host immune system leading to cancer development in FA patients. In this review, we summarize recent advances in unraveling the molecular mechanisms of FA susceptibility to HPV-induced cancers, which facilitate rational preventive and therapeutic strategies.
范可尼贫血症（FA）是一种与染色体脆弱性相关的罕见隐性疾病。FA 患者患癌症的风险非常高，尤其是头颈部鳞状细胞癌和由人乳头瘤病毒（HPV）感染引起的鳞状细胞癌。HPV 致癌基因 E6 和 E7 通过整合到宿主基因组中，导致基因组不稳定性，从而促进 FA 患者致癌所需的 DNA 损伤和基因突变。此外，E6 和 E7 癌蛋白不仅抑制 p53 和视网膜母细胞瘤，还会损害 FANC/BRCA 信号通路，以防止 DNA 损伤修复，并改变包括细胞周期检查点、端粒功能、细胞增殖和干扰宿主免疫系统在内的多种信号，导致 FA 患者癌症的发生。在这篇综述中，我们总结了阐明 FA 易感性 HPV 诱导癌症的分子机制的最新进展，这有助于制定合理的预防和治疗策略。
