{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kent A"],"funding":["United States - Israel Binational Science Foundation (BSF)","Cancer Research UK","NIAID NIH HHS","Robert Wood Johnson Foundation (RWJF)","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)","Division of Intramural Research, National Institute of Allergy and Infectious Diseases","Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)","Division of Cancer Prevention, National Cancer Institute (NCI Division of Cancer Prevention)","United States - Israel Binational Science Foundation","NIDDK NIH HHS","Medical Research Council","NCI NIH HHS","Division of Cancer Prevention, National Cancer Institute","Wellcome Trust","Robert Wood Johnson Foundation","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["53-67"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618359"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(1)"],"pubmed_abstract":["The inflammasome plays multifaceted roles in cancer, but less is known about its function during premalignancy upon initial cell transformation. We report a homeostatic function of the inflammasome in suppressing malignant transformation through Ras inhibition. We identified increased hematopoietic stem cell (HSC) proliferation within the bone marrow of inflammasome-deficient mice. HSCs within an inflammasome-deficient stroma expressed a Ras signature associated with increased Ras pathway- and cancer-related transcripts and heightened levels of cytokine, chemokine and growth factor receptors. Stromal inflammasome deficiency established a poised Ras-dependent mitogenic state within HSCs, which fueled progeny B cell lymphomagenesis upon Myc deregulation in a spontaneous model of B cell lymphoma, and shortened its premalignant stage leading to faster onset of malignancy. Thus, the stromal inflammasome preserves tissue balance by restraining Ras to disrupt the most common oncogenic Myc-Ras cooperation and establish a natural defense against transition to malignancy. These findings should inform preventative therapies against hematological malignancies."],"journal":["Nature immunology"],"pubmed_title":["A stromal inflammasome Ras safeguard against Myc-driven lymphomagenesis."],"pmcid":["PMC7618359"],"funding_grant_id":["T32 AI007605","T32DK116970","2021299","A29210","74260","R21 AI159772","29210","R01 AI170832","R01 AI170897","AI159772","F30 CA174313","AI170897","CC2229","AI170832","AI178327","T32 DK116970","T32AI007605","R21 AI178327"],"pubmed_authors":["Yee Mon KJ","Barbet G","Putzel G","Grier A","Jia B","Evan GI","Kortlever RM","Zhigarev D","Blander JM","Kent A","Hutchins Z"],"additional_accession":[]},"is_claimable":false,"name":"A stromal inflammasome Ras safeguard against Myc-driven lymphomagenesis.","description":"The inflammasome plays multifaceted roles in cancer, but less is known about its function during premalignancy upon initial cell transformation. We report a homeostatic function of the inflammasome in suppressing malignant transformation through Ras inhibition. We identified increased hematopoietic stem cell (HSC) proliferation within the bone marrow of inflammasome-deficient mice. HSCs within an inflammasome-deficient stroma expressed a Ras signature associated with increased Ras pathway- and cancer-related transcripts and heightened levels of cytokine, chemokine and growth factor receptors. Stromal inflammasome deficiency established a poised Ras-dependent mitogenic state within HSCs, which fueled progeny B cell lymphomagenesis upon Myc deregulation in a spontaneous model of B cell lymphoma, and shortened its premalignant stage leading to faster onset of malignancy. Thus, the stromal inflammasome preserves tissue balance by restraining Ras to disrupt the most common oncogenic Myc-Ras cooperation and establish a natural defense against transition to malignancy. These findings should inform preventative therapies against hematological malignancies.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-05T16:38:10.664Z","creation":"2026-06-05T03:06:16.574Z"},"accession":"S-EPMC7618359","cross_references":{"pubmed":["39747433"],"doi":["10.1038/s41590-024-02028-z"]}}