Live cell, image-based high-throughput screen to quantitate p53 stabilization and viability in human papillomavirus positive cancer cells.
Live cell, image-based high-throughput screen to quantitate p53 stabilization and viability in human papillomavirus positive cancer cells.
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DOI：
10.1016/j.virol.2021.05.006
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发表时间：
2021-08
期刊：
影响因子：
3.7
通讯作者：
Howley PM
中科院分区：
文献类型：
--
作者：
Martínez-Noël G;Vieira VC;Szajner P;Lilienthal EM;Kramer RE;Boyland KA;Smith JA;Howley PM
大约5%的癌症是由高危人类乳头瘤病毒引起的。尽管非常有效的预防性疫苗将在未来几十年内显着降低这种癌症负担，但它们对那些已经感染并仍有hrHPV病变恶性进展风险的人没有治疗作用。HPV相关癌症依赖于病毒E6和E7癌基因的表达。hrHPV E6的致癌功能部分依赖于其诱导p53降解的能力。由于p53在hrHPV相关癌症中通常是野生型，p53稳定化阻止增殖，诱导凋亡和/或导致衰老。在这里，我们描述了一个活细胞，基于图像的高通量筛选，以确定稳定p53和/或影响HPV阳性癌症HeLa细胞的活力的化合物。我们通过评估大约6，500种已知生物活性化合物的活性来验证这种筛选试验的稳健性和潜力，说明其作为识别hrHPV新型疗法的平台的能力。
Approximately 5% of cancers are caused by high-risk human papillomaviruses. Although very effective preventive vaccines will reduce this cancer burden significantly over the next several decades, they have no therapeutic effect for those already infected and remaining at risk for malignant progression of hrHPV lesions. HPV-associated cancers are dependent upon the expression of the viral E6 and E7 oncogenes. The oncogenic function of hrHPV E6 relies partially on its ability to induce p53 degradation. Since p53 is generally wildtype in hrHPV-associated cancers, p53 stabilization arrests proliferation, induces apoptosis and/or results in senescence. Here we describe a live cell, image-based high-throughput screen to identify compounds that stabilize p53 and/or affect viability in HPV-positive cancer HeLa cells. We validate the robustness and potential of this screening assay by assessing the activities of approximately 6,500 known bioactive compounds, illustrating its capability to function as a platform to identify novel therapeutics for hrHPV.
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