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Dysregulation of Stemness Pathways in HPV Mediated Cervical Malignant Transformation Identifies Potential Oncotherapy Targets.
Frontiers in Cellular and Infection Microbiology ( IF 5.7 ) Pub Date : 2020-05-20 , DOI: 10.3389/fcimb.2020.00307
Megha Budhwani 1 , Samuel W Lukowski 2 , Sandro V Porceddu 3, 4 , Ian H Frazer 1 , Janin Chandra 1
Affiliation  

Human papillomavirus (HPV) infection is associated with a range of malignancies that affect anogenital and oropharyngeal sites. α-HPVs dominantly infect basal epithelial cells of mucosal tissues, where they dysregulate cell division and local immunity. The cervix is one of the mucosal sites most susceptible to HPV infections. It consists of anatomically diverse regions, and the majority of cervical intraepithelial neoplasia and cancers arise within the cervical squamo-columnar junction where undifferentiated basal progenitor cells with stem cell properties are found. The cancer stem cell theory particularly associates tumorigenesis, invasion, dissemination, and metastasis with cancer cells exhibiting stem cell properties. In this perspective, we discuss evidence of a cervical cancer stem cell niche and explore the association of stemness related genes with 5-year survival using a publicly available transcriptomic dataset of a cervical cancer cohort. We report that poor prognosis in this cohort correlates with overexpression of a subset of stemness pathway genes, a majority of which regulate the central Focal Adhesion pathway, and are also found to be enriched in the HPV infection pathway. These observations support therapeutic targeting of stemness genes overexpressed by mucosal cells infected with high-risk HPVs.



中文翻译:

HPV介导的宫颈恶性转化中茎通路的失调可确定潜在的肿瘤治疗靶标。

人乳头瘤病毒(HPV)感染与影响肛门生殖器和口咽部位的一系列恶性肿瘤有关。α-HPV主要感染粘膜组织的基底上皮细胞,并在那里异常调节细胞分裂和局部免疫。子宫颈是最易感染HPV的粘膜部位之一。它由解剖学上不同的区域组成,并且大多数宫颈上皮内瘤变和癌症发生在宫颈鳞状-柱状交界处,在该处发现了未分化的具有干细胞特性的基础祖细胞。癌症干细胞理论特别将肿瘤的发生,侵袭,扩散和转移与表现出干细胞特性的癌细胞联系起来。从这个角度来看,我们讨论了子宫颈癌干细胞生态位的证据,并使用子宫颈癌队列的公开转录组数据集探讨了与干性相关的基因与5年生存率的关系。我们报告说,该队列的不良预后与干途径基因的一个子集的过表达有关,其中大部分基因调节中央局灶性黏附途径,并且也被发现富含HPV感染途径。这些观察结果支持了针对被高危HPV感染的粘膜细胞过度表达的干基因的治疗靶向。其中大多数可调节中央局灶性黏附途径,并且还发现其富含HPV感染途径。这些观察结果支持了由高危HPV感染的粘膜细胞过度表达的干基因的治疗靶向。其中大多数可调节中央局灶性黏附途径,并且还发现其富含HPV感染途径。这些观察结果支持了由高危HPV感染的粘膜细胞过度表达的干基因的治疗靶向。

更新日期:2020-06-25
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