Crosstalk Between the Oncoproteins of High‐Risk Human Papillomaviruses Types 16 and 18 in Colorectal Cancer Cell Models

ABSTRACT Background 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 canc...

Full description

Saved in:
Bibliographic Details
Main Authors: Queenie Fernandes, Varghese Philipose Inchakalody, Sarra Mestiri, Takwa Bedhiafi, Shereena Hydrose, Sara S. Bashraheel, Maysaloun Merhi, Said Dermime, Ala‐Eddin Al Moustafa
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Cancer Reports
Subjects:
Online Access:https://doi.org/10.1002/cnr2.70197
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:ABSTRACT Background 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. Aims 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. Methods 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. Results 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. Conclusion 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.
ISSN:2573-8348