{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["17(3)"],"submitter":["Zhao Q"],"pubmed_abstract":["Mixed lineage kinase domain-like protein (MLKL) plays an important role in necroptosis, but the role and mechanism of MLKL in intestinal tumorigenesis remain unclear. Here, we found that hematopoietic- and nonhematopoietic-derived MLKL affected intestinal inflammation, but nonhematopoietic-derived MLKL primarily inhibited intestinal tumorigenesis. Loss of MLKL enhanced intestinal regeneration and the susceptibility to intestinal tumorigenesis in <i>Apc<sup>min/+</sup></i> mice by hyperactivating the Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) axis. Furthermore, MLKL deficiency increased interleukin-6 (IL-6) production in dendritic cells. Administration of anti-IL-6R antibody therapy reduced intestinal tumorigenesis in <i>Apc<sup>min/+</sup>Mlkl<sup>-/-</sup></i> mice. Notably, low MLKL expression in human colorectal tumors, which enhanced STAT3 activation, was associated with decreased overall survival. Together, our results reveal that MLKL exhibits a suppressive effect during intestinal tumorigenesis by suppressing the IL-6/JAK2/STAT3 signals."],"journal":["International journal of biological sciences"],"pagination":["869-881"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7975698"],"repository":["biostudies-literature"],"pubmed_title":["MLKL inhibits intestinal tumorigenesis by suppressing STAT3 signaling pathway."],"pmcid":["PMC7975698"],"pubmed_authors":["Guo Y","Jin S","Cheng X","Liu Y","Guo J","Zhao Q","Ren J","Zhang X","Tan Y","Kuang L","Zhong J","Pan L","Yu X","Bi Y"],"additional_accession":[]},"is_claimable":false,"name":"MLKL inhibits intestinal tumorigenesis by suppressing STAT3 signaling pathway.","description":"Mixed lineage kinase domain-like protein (MLKL) plays an important role in necroptosis, but the role and mechanism of MLKL in intestinal tumorigenesis remain unclear. Here, we found that hematopoietic- and nonhematopoietic-derived MLKL affected intestinal inflammation, but nonhematopoietic-derived MLKL primarily inhibited intestinal tumorigenesis. Loss of MLKL enhanced intestinal regeneration and the susceptibility to intestinal tumorigenesis in <i>Apc<sup>min/+</sup></i> mice by hyperactivating the Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) axis. Furthermore, MLKL deficiency increased interleukin-6 (IL-6) production in dendritic cells. Administration of anti-IL-6R antibody therapy reduced intestinal tumorigenesis in <i>Apc<sup>min/+</sup>Mlkl<sup>-/-</sup></i> mice. Notably, low MLKL expression in human colorectal tumors, which enhanced STAT3 activation, was associated with decreased overall survival. Together, our results reveal that MLKL exhibits a suppressive effect during intestinal tumorigenesis by suppressing the IL-6/JAK2/STAT3 signals.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021","modification":"2025-04-18T16:03:30.952Z","creation":"2025-04-07T02:59:19.318Z"},"accession":"S-EPMC7975698","cross_references":{"pubmed":["33767595"],"doi":["10.7150/ijbs.56152"]}}