TY - JOUR
T1 - Coxsackievirus and adenovirus receptor expression facilitates enteroviral infections to drive the development of pancreatic cancer
AU - Bastea, Ligia I.
AU - Liu, Xiang
AU - Fleming, Alicia K.
AU - Pandey, Veethika
AU - Döppler, Heike
AU - Edenfield, Brandy H.
AU - Krishna, Murli
AU - Zhang, Lizhi
AU - Thompson, E. Aubrey
AU - Grandgenett, Paul M.
AU - Hollingsworth, Michael A.
AU - Fairweather, De Lisa
AU - Clemens, Dahn
AU - Storz, Peter
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-024-55043-x
DO - 10.1038/s41467-024-55043-x
M3 - Article
C2 - 39627248
AN - SCOPUS:85211350647
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 10547
ER -