RT Journal Article
SR Electronic
T1 Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201494
DO 10.26508/lsa.202201494
VO 6
IS 4
A1 Bodnar-Wachtel, Mélanie
A1 Huber, Anne-Laure
A1 Gorry, Julie
A1 Hacot, Sabine
A1 Burlet, Delphine
A1 Gérossier, Laetitia
A1 Guey, Baptiste
A1 Goutagny, Nadège
A1 Bartosch, Birke
A1 Ballot, Elise
A1 Lecuelle, Julie
A1 Truntzer, Caroline
A1 Ghiringhelli, François
A1 Py, Bénédicte F
A1 Couté, Yohann
A1 Ballesta, Annabelle
A1 Lantuejoul, Sylvie
A1 Hall, Janet
A1 Tissier, Agnès
A1 Petrilli, Virginie
YR 2023
UL https://www.life-science-alliance.org/content/6/4/e202201494.abstract
AB NLRP3 is a pattern recognition receptor with a well-documented role in inducing inflammasome assembly in response to cellular stress. Deregulation of its activity leads to many inflammatory disorders including gouty arthritis, Alzheimer disease, and cancer. Whereas its role in the context of cancer has been mostly explored in the immune compartment, whether NLRP3 exerts functions unrelated to immunity in cancer development remains unexplored. Here, we demonstrate that NLRP3 interacts with the ATM kinase to control the activation of the DNA damage response, independently of its inflammasome activity. NLRP3 down-regulation in both broncho- and mammary human epithelial cells significantly impairs ATM pathway activation, leading to lower p53 activation, and provides cells with the ability to resist apoptosis induced by acute genotoxic stress. Interestingly, NLRP3 expression is down-regulated in non-small cell lung cancers and breast cancers, and its expression positively correlates with patient overall survival. Our findings identify a novel non-immune function for NLRP3 in maintaining genome integrity and strengthen the concept of a functional link between innate immunity and DNA damage sensing pathways to maintain cell integrity.