人乳头瘤病毒(HPV)的致癌基因E6和E7的转录受病毒基因组的长控制区(LCR)的调控。虽然已经报道了各种转录因子与LCR的结合，但对于与这些转录因子共同调节HPV致癌基因表达的转录辅助因子知之甚少。在这里，我们在宫颈癌细胞中通过体外DNA-拉蛋白纯化，然后进行蛋白质组学分析，以识别通过转录因子TEAD1结合到HPV16 LCR的转录辅助因子。我们检测到前炎症因子S100A9定位在宫颈癌细胞的细胞核中，并与LCR通过直接与TEAD1相互作用形成关联。前炎症因子S100A9的核表达水平以及其与LCR的关联通过前炎症榄香酯的处理在宫颈癌细胞中增加。S100A9的沉默减少了HPV致癌基因的表达，并减少了宫颈癌细胞的生长以及对顺铂的敏感性，而通过核定位信号强迫核内表达S100A9则产生了相反的效果。因此，我们得出结论，核型S100A9通过TEAD1与HPV LCR结合，并通过作为转录共激活因子来增强病毒致癌基因的表达。 重要性：人乳头瘤病毒(HPV)感染是宫颈癌的主要原因，其中致癌基因E6和E7在肿瘤发生中起着重要作用。虽然宫颈炎症是宫颈癌发生的原因之一，但这些炎症反应在HPV致癌过程中的分子机制尚未完全理解。我们的研究表明，炎症刺激能诱导产生前炎症因子S100A9在宫颈癌细胞的细胞核内，并通过作为TEAD1的转录共激活因子来增强HPV致癌基因的表达。这些发现为炎症和病毒致癌之间的关系提供了新的分子认识。

Transcription of the human papillomavirus (HPV) oncogenes, E6 and E7, is regulated by the long control region (LCR) of the viral genome. Although various transcription factors have been reported to bind to the LCR, little is known about the transcriptional cofactors that modulate HPV oncogene expression in association with these transcription factors. Here, we performed in vitro DNA-pulldown purification of nuclear proteins in cervical cancer cells, followed by proteomic analyses to identify transcriptional cofactors that bind to the HPV16 LCR via the transcription factor TEAD1. We detected the proinflammatory cytokine S100A9 that localized to the nucleus of cervical cancer cells and associated with the LCR via direct interaction with TEAD1. Nuclear S100A9 levels and its association with the LCR were increased in cervical cancer cells by treatment with a proinflammatory phorbol ester. Knockdown of S100A9 decreased HPV oncogene expression and reduced the growth of cervical cancer cells and their susceptibility to cisplatin, whereas forced nuclear expression of S100A9 using nuclear localization signals exerted opposite effects. Thus, we conclude that nuclear S100A9 binds to the HPV LCR via TEAD1 and enhances viral oncogene expression by acting as a transcriptional coactivator. IMPORTANCE Human papillomavirus (HPV) infection is the primary cause of cervical cancer, and the viral oncogenes E6 and E7 play crucial roles in carcinogenesis. Although cervical inflammation contributes to the development of cervical cancer, the molecular mechanisms underlying the role of these inflammatory responses in HPV carcinogenesis are not fully understood. Our study shows that S100A9, a proinflammatory cytokine, is induced in the nucleus of cervical cancer cells by inflammatory stimuli, and it enhances HPV oncogene expression by acting as a transcriptional coactivator of TEAD1. These findings provide new molecular insights into the relationship between inflammation and viral carcinogenesis.