Fernandes Queenie, Inchakalody Varghese Philipose, Mestiri Sarra, Bedhiafi Takwa, Hydrose Shereena, Bashraheel Sara S, Merhi Maysaloun, Dermime Said, Al Moustafa Ala-Eddin
College of Medicine, QU Health, Qatar University, Doha, Qatar.
Translational Cancer Research Facility, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar.
Cancer Rep (Hoboken). 2025 Jun;8(6):e70197. doi: 10.1002/cnr2.70197.
Colorectal cancer (CRC) represents a major fraction of the total cancer burden worldwide. It has been recently identified that various high-risk Human Papillomaviruses (HPVs) are present in human CRCs, where they play a critical role in the development and progression of the cancer.
In this study, we explored the synergistic effect of the E6/E7 viral oncoproteins of the two most frequently observed HPV types (16 and 18) on KRAS and TP53 mutant CRC cell models.
We performed an experimental in vitro study utilizing lipofection to transfect KRAS and TP53 mutant CRC cell models (HCT 116 and HT-29 respectively) with E6/E7 oncoproteins of HPV types 16 and 18 individually and in combination. Subsequently, we assessed their synergistic effect on cell proliferation, invasion, migration, and survival. In addition, we also compared the protein expression patterns of key epithelial-mesenchymal transition (EMT) biomarkers like E-cadherin, fascin, and vimentin among transfected, co-transfected, and wild-type cells.
We found that the co-expression of E6/E7 of HPV types 16 and 18 enhanced cell proliferation, invasion, migration, and survival in both cell models. Interestingly, this was also accompanied by the deregulation of all three EMT biomarkers, E-cadherin, fascin, and vimentin. The synergistic effect of the viral oncoproteins in promoting cancer was more pronounced in TP53 mutant cells (HT-29) as compared to KRAS mutant cells (HCT 116). We also report that HPV type 18 can induce a greater and more sustained oncogenic outcome as compared to HPV type 16.
Our data indicate that co-expression of the E6/E7 oncoproteins of HPV types 16 and 18 can enhance oncogenic processes in CRC, especially TP53 mutant CRC.
结直肠癌（CRC）是全球癌症总负担的主要组成部分。最近发现，多种高危型人乳头瘤病毒（HPV）存在于人类结直肠癌中，它们在癌症的发生和发展中起关键作用。
在本研究中，我们探讨了两种最常见的HPV类型（16型和18型）的E6/E7病毒癌蛋白对KRAS和TP53突变的结直肠癌细胞模型的协同作用。
我们进行了一项体外实验研究，利用脂质体转染法分别或联合用16型和18型HPV的E6/E7癌蛋白转染KRAS和TP53突变的结直肠癌细胞模型（分别为HCT 116和HT-29）。随后，我们评估了它们对细胞增殖、侵袭、迁移和存活的协同作用。此外，我们还比较了转染、共转染和野生型细胞中关键上皮-间质转化（EMT）生物标志物（如E-钙黏蛋白、成束蛋白和波形蛋白）的蛋白表达模式。
我们发现，16型和18型HPV的E6/E7共表达增强了两种细胞模型中的细胞增殖、侵袭、迁移和存活。有趣的是，这还伴随着所有三种EMT生物标志物E-钙黏蛋白、成束蛋白和波形蛋白的失调。与KRAS突变细胞（HCT 116）相比，病毒癌蛋白在促进癌症方面的协同作用在TP53突变细胞（HT-29）中更为明显。我们还报告说，与16型HPV相比，18型HPV能诱导更大且更持久的致癌结果。
我们的数据表明，16型和18型HPV的E6/E7癌蛋白共表达可增强结直肠癌，尤其是TP53突变型结直肠癌中的致癌过程。
