Coxsackievirus and adenovirus receptor expression facilitates enteroviral infections to drive the development of pancreatic cancer
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.
Authors
- Michael Anthony Hollingsworth (ORCID: https://orcid.org/0000-0002-5255-8888)
- E. Aubrey Thompson (ORCID: https://orcid.org/0000-0002-9001-4240)
- Heike Döppler
- Brandy Edenfield (ORCID: https://orcid.org/0009-0005-5571-9500)
- Alicia K. Fleming Martinez (ORCID: https://orcid.org/0000-0003-0319-9994)
- Peter Störz (ORCID: https://orcid.org/0000-0002-0132-5128)
- Ligia I. Bastea (ORCID: https://orcid.org/0000-0001-9542-7186)
- DeLisa Fairweather (ORCID: https://orcid.org/0000-0003-3093-1810)
- Veethika Pandey (ORCID: https://orcid.org/0000-0002-1476-2124)
- Murli Krishna (ORCID: https://orcid.org/0000-0001-8763-0168)
- Paul M. Grandgenett (ORCID: https://orcid.org/0000-0002-6905-1805)
- Lizhi Zhang (ORCID: https://orcid.org/0000-0001-5829-9234)
- Dahn L. Clemens
- Xiang Liu (ORCID: https://orcid.org/0000-0001-7682-6886)
Institutions
- Jacksonville College (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic in Florida (US)
- University of Nebraska Medical Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-04
- DOI
- https://doi.org/10.1038/s41467-024-55043-x
- Citations
- 6
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 3.30
Funders
- National Institutes of Health
- Center for Individualized Medicine, Mayo Clinic
- National Cancer Institute