Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis.

ABSTRACT: Cancer-associated systemic inflammation is strongly linked to poor disease outcome in patients with cancer^1,2. For most human epithelial tumour types, high systemic neutrophil-to-lymphocyte ratios are associated with poor overall survival³, and experimental studies have demonstrated a causal relationship between neutrophils and metastasis^4,5. However, the cancer-cell-intrinsic mechanisms that dictate the substantial heterogeneity in systemic neutrophilic inflammation between tumour-bearing hosts are largely unresolved. Here, using a panel of 16 distinct genetically engineered mouse models for breast cancer, we uncover a role for cancer-cell-intrinsic p53 as a key regulator of pro-metastatic neutrophils. Mechanistically, loss of p53 in cancer cells induced t

SUBMITTER: Wellenstein MD 

PROVIDER: S-EPMC6707815 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature