Splicing of HPV16 E6 promotes aggressive invasion in oropharyngeal cancer via endocytosis of E-cadherin.

ABSTRACT: Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) is now the leading HPV+ cancer in the United States and United Kingdom. Despite high cure rates, a significant subset of patients have aggressive HPV+ OPSCC that recurs; deciphering the underlying mechanisms will identify biomarkers that delineate patient subgroups for personalized treatment. In a comprehensive investigation using complementary clinically-relevant models of HPV+ OPSCC, we demonstrated that elevated expression of a HPV16 E6 spliced isoform (E6*I) compared to full-length E6 (E6FL), is critical for aggressive invasion. Introduction of splice switching oligonucleotides (SSOs) to inhibit E6FL splicing, effectively mitigated invasion. Mechanistic studies revealed that aggressive invasion occurs via

SUBMITTER: Lim YX 

PROVIDER: S-EPMC12632831 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature