Human Papillomavirus 16 E6 Suppresses Transporter Associated with Antigen-Processing Complex in Human Tongue Keratinocyte Cells by Activating Lymphotoxin Pathway
Issued Date
2022-04-01
Resource Type
eISSN
20726694
Scopus ID
2-s2.0-85127963270
Journal Title
Cancers
Volume
14
Issue
8
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cancers Vol.14 No.8 (2022)
Suggested Citation
Burassakarn A., Phusingha P., Yugawa T., Noguchi K., Ekalaksananan T., Vatanasapt P., Kiyono T., Pientong C. Human Papillomavirus 16 E6 Suppresses Transporter Associated with Antigen-Processing Complex in Human Tongue Keratinocyte Cells by Activating Lymphotoxin Pathway. Cancers Vol.14 No.8 (2022). doi:10.3390/cancers14081944 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83776
Title
Human Papillomavirus 16 E6 Suppresses Transporter Associated with Antigen-Processing Complex in Human Tongue Keratinocyte Cells by Activating Lymphotoxin Pathway
Other Contributor(s)
Abstract
Infection by high-risk human papillomaviruses (hrHPVs), including HPV type 16 (HPV16), is a major risk factor for oral squamous cell carcinomas (OSCCs). However, the pathogenic mechanism by which hrHPVs promote oral carcinogenesis remains to be elucidated. Here, we demonstrated that the suppression of a transporter associated with the antigen-processing complex (TAPs; TAP1 and TAP2), which is a key molecule in the transportation of viral antigenic peptides into MHC class-I cells, is affected by the E6 protein of HPV16. Mechanistically, HPV-mediated immune evasion is principally mediated via the signal-transduction network of a lymphotoxin (LT) pathway, in particular LTα1 β2 and LTβR. Our analysis of transcriptomic data from an HNSCC cohort from the Cancer Genome Atlas (TCGA) indicated that expression of TAP genes, particularly TAP2, was downregulated in HPV-infected cases. We further demonstrated that LTα1 β2 and LTβR were upregulated, which was negatively correlated with TAP1 and TAP2 expression in HPV-positive clinical OSCC samples. Taken together, our findings imply that HPV16 E6 regulates the machinery of the antigenic peptide-loading system and helps to clarify the role of oncogenic viruses in the context of oral carcinoma.