HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1.

HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1.
Autophagy. 2020 Nov 10;:
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 GM
Abstract
Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favourable 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.
PMID: 33172332 [PubMed -...

Source: Autophagy - November 10, 2020 Category: Cytology 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 GM Tags: Autophagy Source Type: research