{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Boutet M"],"funding":["NIAID NIH HHS","NCI NIH HHS","NIGMS NIH HHS","NIH HHS"],"pagination":["2035-2053.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12344594"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["58(8)"],"pubmed_abstract":["Loss-of-function mutations in MLL3, encoding the histone methyltransferase MLL3/KMT2C, are frequent in various cancer types. To examine the mechanisms whereby MLL3 suppresses tumorigenesis, we developed a mouse mammary-stem-cell-based tumor model bearing cancer-driver mutations, including loss of MLL3/KMT2C and p53 and constitutive phosphatidylinositol 3-kinase (PI3K) activation, recapitulating a genetic makeup of aggressive human breast cancers. MLL3 loss stabilized the transcription factor HIF1α, which increased secretion of the chemokine CCL2 by tumor cells and promoted recruitment of CCR2<sup>+</sup> regulatory T (Treg) cells. Treg cell depletion slowed tumor onset and progression. In human breast tumors, infiltration of Treg cells correlated with the presence of MLL3 mutations. HIF1α "],"journal":["Immunity"],"pubmed_title":["Mutations in MLL3 promote breast cancer progression via HIF1α-dependent intratumoral recruitment and differentiation of regulatory T cells."],"pmcid":["PMC12344594"],"funding_grant_id":["R56 AI103338","P30 CA013330","R25 GM104547","T32 GM007288","R01 AI103338","R01 CA212424","S10 OD026852"],"pubmed_authors":["Suzuki M","Fineberg SA","Couturier N","Guo W","Leavenworth JW","Erler P","Barbieux E","Militello AM","Coutinho De Miranda M","Boutet M","Zhang Z","Guillen E","Lu J","Montagna C","Lauvau G","Mani SA","Nishitani K","Sparano JA","Wang Y"],"additional_accession":[]},"is_claimable":false,"name":"Mutations in MLL3 promote breast cancer progression via HIF1α-dependent intratumoral recruitment and differentiation of regulatory T cells.","description":"Loss-of-function mutations in MLL3, encoding the histone methyltransferase MLL3/KMT2C, are frequent in various cancer types. To examine the mechanisms whereby MLL3 suppresses tumorigenesis, we developed a mouse mammary-stem-cell-based tumor model bearing cancer-driver mutations, including loss of MLL3/KMT2C and p53 and constitutive phosphatidylinositol 3-kinase (PI3K) activation, recapitulating a genetic makeup of aggressive human breast cancers. MLL3 loss stabilized the transcription factor HIF1α, which increased secretion of the chemokine CCL2 by tumor cells and promoted recruitment of CCR2<sup>+</sup> regulatory T (Treg) cells. Treg cell depletion slowed tumor onset and progression. In human breast tumors, infiltration of Treg cells correlated with the presence of MLL3 mutations. HIF1α ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-29T17:35:12.779Z","creation":"2026-04-08T05:37:12.639Z"},"accession":"S-EPMC12344594","cross_references":{"pubmed":["40749665"],"doi":["10.1016/j.immuni.2025.07.008"]}}