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However, the functional role for these proteins remains unproven.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The putative tumour suppressor role of\n                      <jats:italic>Runx1<\/jats:italic>\n                      was investigated in genetic mouse models of breast cancer. Stem cell assays, immunohistochemistry and RNAseq analyses were applied to study biological and molecular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Runx1<\/jats:italic>\n                      loss of function leads to accelerated disease onset and tumour development in breast cancer models. Combined deletion of\n                      <jats:italic>Runx1<\/jats:italic>\n                      and\n                      <jats:italic>Runx2<\/jats:italic>\n                      further resulted in mammary cells becoming exquisitely sensitive to WNT-driven transformation, with expedited emergence of multiple tumours.\n                      <jats:italic>Runx1<\/jats:italic>\n                      ablation induces a stem cell-like phenotype in mammary epithelial cells, whilst transcriptomic analysis demonstrated activation of multiple oncogenic pathways, especially when\n                      <jats:italic>Runx2<\/jats:italic>\n                      was co-deleted. Altered\n                      <jats:italic>Runx<\/jats:italic>\n                      expression in the mammary epithelium also drove alterations in the tumour immune microenvironment, with changes to neutrophil and macrophage populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Runx1<\/jats:italic>\n                      restricts some forms of breast cancer and inhibits the full oncogenic potential of aberrant WNT signalling. Combined\n                      <jats:italic>Runx1<\/jats:italic>\n                      and\n                      <jats:italic>Runx2<\/jats:italic>\n                      loss dramatically accelerates disease progression suggesting that\n                      <jats:italic>Runx2<\/jats:italic>\n                      can substitute for\n                      <jats:italic>Runx1<\/jats:italic>\n                      in dampening the oncogenic effects of WNT signalling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03439-5","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T01:23:15Z","timestamp":1778116995000},"page":"532-545","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Runx1 and Runx2 act in concert to suppress Wnt\/\u03b2-catenin-driven mammary 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