| First Author | Zhao Q | Year | 2021 |
| Journal | Int J Biol Sci | Volume | 17 |
| Issue | 3 | Pages | 869-881 |
| PubMed ID | 33767595 | Mgi Jnum | J:308937 |
| Mgi Id | MGI:6753561 | Doi | 10.7150/ijbs.56152 |
| Citation | Zhao Q, et al. (2021) MLKL inhibits intestinal tumorigenesis by suppressing STAT3 signaling pathway. Int J Biol Sci 17(3):869-881 |
| abstractText | 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 Apc(min/+) 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 Apc(min/+)Mlkl(-/-) 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. |
