Nature: p53 deletion leads to breast cancer metastasis through systemic inflammation

August 6, 2019 / bioin / - cancer related systemic inflammation is closely related to poor prognosis of cancer patients For most human epithelial tumor types, the high ratio of neutrophils to lymphocytes in the system is related to the poor overall survival rate Experimental studies show that there is a causal relationship between neutrophils and metastasis However, up to now, it is not clear that the intrinsic mechanism of tumor cells determines the heterogeneity of systemic neutrophil inflammation in cancer patients To this end, researchers from the Netherlands Cancer Research Institute and other units used 16 different breast cancer genetic engineering mouse models to reveal the role of p53 inherent in cancer cells as a key regulator of metastatic neutrophils Photo source: nature researchers found that in terms of mechanism, the loss of p53 in cancer cells can induce the secretion of Wnt ligand, which can stimulate tumor related macrophages to produce IL-1 β, thus promoting systemic inflammation Inhibition of Wnt secretion by p53 deficient cancer cells by pharmacological and genetic means can reverse the production of IL-1 β by macrophages and inhibit subsequent neutrophil inflammation, thus reducing the formation of metastasis In general, researchers have shown a mechanism for the loss of p53, the secretion of Wnt ligands, and systemic neutropenia in cancer cells, which can accelerate metastasis These findings clarify the importance of breast cancer gene composition in determining metastatic systemic inflammation and lay a foundation for individualized immune intervention strategies for cancer patients Reference: Karin E de Visser et al Loss of p53 triggers Wnt dependent system information to drive breast cancer metadata Nature DOI https://doi.org/10.1038/s41586-019-1450-6