Abstract：
Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.
摘要：
食管鳞状细胞癌（ESCC）可能与HPV感染有关，HPV16感染诱导ESCC形成的潜在机制仍然难以捉摸。这里,我们过表达HPV16E6和E7，并协调了这两个基因在EPC2和ESCC细胞中的过表达。我们发现E7和E6、E7的协同表达促进了EPC2细胞的增殖,由于使用vismodegib导致类器官形成失败，因此shh的上调是细胞增殖的原因。同时,E6和E7在ESCC细胞中的过表达促进细胞增殖，迁移,和体外侵袭。重要的是,E6和E7协同增加裸鼠的肿瘤生长能力，而vismodegib减缓了NCG小鼠肿瘤的生长。此外，E6和E7基因过表达后，细胞系中的一系列基因和蛋白质发生了变化，使用生物信息学分析系统分析了潜在的生物过程和途径.一起,这些发现表明，HPV16感染诱导的hedgehog途径的激活可能最初会转化食管中的基底细胞，并促进ESCC细胞的恶性过程。刺猬抑制剂的应用可以代表ESCC治疗的治疗途径。
