Role of iqgap1 in papillomavirus-associated head and neck tumorigenesis

Tao Wei, Suyong Choi, Darya Buehler, Denis Lee, Ella Ward-Shaw, Richard A. Anderson, Paul F. Lambert

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Approximately 25% of head and neck squamous cell carcinomas (HNSCC) are associated with human papillomavirus (HPV) infection. In these cancers as well as in HPV-associated anogen-ital cancers, PI3K signaling is highly activated. We previously showed that IQ motif-containing GTPase activating protein 1 (IQGAP1), a PI3K pathway scaffolding protein, is overexpressed in and contributes to HNSCC and that blocking IQGAP1-mediated PI3K signaling reduces HPV-positive HN-SCC cell survival and migration. In this study, we tested whether IQGAP1 promotes papillomavirus (PV)-associated HNSCCs. IQGAP1 was necessary for optimal PI3K signaling induced by HPV16 oncoproteins in transgenic mice and MmuPV1 infection, a mouse papillomavirus that causes HN-SCC in mice. Furthermore, we found that, at 6 months post-infection, MmuPV1-infected Iqgap1−/− mice developed significantly less severe tumor phenotypes than MmuPV1-infected Iqgap1+/+ mice, indicating a role of IQGAP1 in MmuPV1-associated HNSCC. The tumors resulting from MmuPV1 infection showed features consistent with HPV infection and HPV-associated cancer. However, such IQGAP1-dependent effects on disease severity were not observed in an HPV16 transgenic mouse model for HNC. This may reflect that IQGAP1 plays a role in earlier stages of viral pathogenesis, or other activities of HPV16 oncogenes are more dominant in driving carcinogenesis than their influence on PI3K signaling.

Original languageEnglish (US)
Article number2276
JournalCancers
Volume13
Issue number9
DOIs
StatePublished - May 1 2021
Externally publishedYes

Keywords

  • HPV
  • Head and neck cancer
  • IQGAP1
  • Infection model
  • MmuPV1
  • Mouse model
  • PI3K signaling
  • Papillomavirus

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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