Senolytic Therapy: A Potential Approach for the Elimination of Oncogene-Induced Senescent HPV-Positive Cells.
Senolytic Therapy: A Potential Approach for the Elimination of Oncogene-Induced Senescent HPV-Positive Cells.
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DOI：
10.3390/ijms232415512
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发表时间：
2022-12-08
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
衰老代表一种独特的细胞应激反应，其特征是稳定的生长停滞、大分子改变和基因表达的广谱变化。传统上，衰老是体细胞重复分裂导致端粒逐渐磨损的最终产物。此外，衰老细胞在癌前病变中积累，部分是癌基因过度激活的产物，反映了衰老的肿瘤抑制功能的一个要素。诱导衰老的致癌过程包括 H-Ras、B-Raf 和细胞周期蛋白 E 的过度表达/过度激活以及 PTEN 的失活。致癌病毒，例如人乳头瘤病毒（HPV），也被证明会诱导衰老。高危 HPV 毒株通过多种机制驱动宫颈上皮细胞的永生化，从而实现转化，但主要是通过细胞周期的失调，也可能是通过促进逃避衰老。尽管 HPV 疫苗在降低宫颈癌发病率方面得到了广泛而成功的利用，但这一措施并不能有效预防 HPV 阳性个体的癌症发展。因此，在这篇评论中，我们重点关注癌基因和 HPV 诱导的衰老 (OIS) 在宫颈癌中的潜在贡献。我们进一步考虑了衰老抑制剂在消除携带 HPV 的衰老细胞方面的潜在效用，作为减少 HPV 驱动的转化和宫颈癌发展风险的策略。
Senescence represents a unique cellular stress response characterized by a stable growth arrest, macromolecular alterations, and wide spectrum changes in gene expression. Classically, senescence is the end-product of progressive telomeric attrition resulting from the repetitive division of somatic cells. In addition, senescent cells accumulate in premalignant lesions, in part, as a product of oncogene hyperactivation, reflecting one element of the tumor suppressive function of senescence. Oncogenic processes that induce senescence include overexpression/hyperactivation of H-Ras, B-Raf, and cyclin E as well as inactivation of PTEN. Oncogenic viruses, such as Human Papilloma Virus (HPV), have also been shown to induce senescence. High-risk strains of HPV drive the immortalization, and hence transformation, of cervical epithelial cells via several mechanisms, but primarily via deregulation of the cell cycle, and possibly, by facilitating escape from senescence. Despite the wide and successful utilization of HPV vaccines in reducing the incidence of cervical cancer, this measure is not effective in preventing cancer development in individuals already positive for HPV. Accordingly, in this commentary, we focus on the potential contribution of oncogene and HPV-induced senescence (OIS) in cervical cancer. We further consider the potential utility of senolytic agents for the elimination of HPV-harboring senescent cells as a strategy for reducing HPV-driven transformation and the risk of cervical cancer development.
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影响因子：
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