| Title: |
HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1 |
| Authors: |
Antonioli M.; Pagni B.; Vescovo T.; Ellis R.; Cosway B.; Rollo F.; Bordoni V.; Agrati C.; Labus M.; Covello R.; Benevolo M.; Ippolito G.; Robinson M.; Piacentini M.; Lovat P.; Fimia G. M. |
| Contributors: |
Antonioli, M.; Pagni, B.; Vescovo, T.; Ellis, R.; Cosway, B.; Rollo, F.; Bordoni, V.; Agrati, C.; Labus, M.; Covello, R.; Benevolo, M.; Ippolito, G.; Robinson, M.; Piacentini, M.; Lovat, P.; Fimia, G. M. |
| Publisher Information: |
Bellwether Publishing, Ltd. |
| Publication Year: |
2021 |
| Collection: |
Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: |
AMBRA1; autophagy; calpain; hpv-E7; oropharyngeal squamous cell carcinoma |
| Description: |
Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favorable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPV-positive OPSCC cells display reduced macroautophagy/autophagy activity, mediated by the ability of HPV-E7 to interact with AMBRA1, to compete with its binding to BECN1 and to trigger its calpain-dependent degradation. Moreover, we have shown that AMBRA1 downregulation and pharmacological inhibition of autophagy sensitized HPV-negative OPSCC cells to the cytotoxic effects of cisplatin. Importantly, semi-quantitative immunohistochemical analysis in primary OPSCCs confirmed that AMBRA1 expression is reduced in HPV-positive compared to HPV-negative tumors. Collectively, these data identify AMBRA1 as a key target of HPV to impair autophagy and propose the targeting of autophagy as a viable therapeutic strategy to improve treatment response of HPV-negative OPSCC. Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; CDDP: cisplatin (CDDP); FFPE: formalin-fixed paraffin-embedded (FFPE); HNC: head and neck cancers (HNC); HPV: human papillomavirus (HPV); hrHPV: high risk human papillomavirus (hrHPV); OCSCC: oral cavity squamous carcinomas (OCSSC); OPSCC: oropharyngeal squamous cell carcinoma (OPSCC); OS: overall survival (OS); qPCR: quantitative polymerase chain reaction; RB1: RB transcriptional corepressor 1; ROC: receiver operating characteristic curve (ROC). |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/33172332; info:eu-repo/semantics/altIdentifier/wos/WOS:000591466900001; volume:17; issue:10; firstpage:2842; lastpage:2855; numberofpages:14; journal:AUTOPHAGY; https://hdl.handle.net/11573/1470019 |
| DOI: |
10.1080/15548627.2020.1847444 |
| Availability: |
https://hdl.handle.net/11573/1470019; https://doi.org/10.1080/15548627.2020.1847444 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.8BFAD4C3 |
| Database: |
BASE |