Coxsackievirus and adenovirus receptor expression facilitates enteroviral infections to drive the development of pancreatic cancer

Ligia I. Bastea, Xiang Liu, Alicia K. Fleming, Veethika Pandey, Heike Döppler, Brandy H. Edenfield, Murli Krishna, Lizhi Zhang, E. Aubrey Thompson, Paul M. Grandgenett, Michael A. Hollingsworth, De Lisa Fairweather, Dahn Clemens, Peter Storz

Research output: Contribution to journalArticlepeer-review

Abstract

The development of pancreatic cancer requires both, acquisition of an oncogenic mutation in KRAS as well as an inflammatory insult. However, the physiological causes for pancreatic inflammation are less defined. We show here that oncogenic KRas-expressing pre-neoplastic lesion cells upregulate coxsackievirus (CVB) and adenovirus receptor (CAR). This facilitates infections from enteroviruses such as CVB3, which can be detected in approximately 50% of pancreatic cancer patients. Moreover, using an animal model we show that a one-time pancreatic infection with CVB3 in control mice is transient, but in the presence of oncogenic KRas drives chronic inflammation and rapid development of pancreatic cancer. We further demonstrate that a knockout of CAR in pancreatic lesion cells blocks these CVB3-induced effects. Our data demonstrate that KRas-caused lesions promote the development of pancreatic cancer by enabling certain viral infections.

Original languageEnglish (US)
Article number10547
JournalNature communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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