| First Author | Ma JF | Year | 2017 |
| Journal | EMBO Mol Med | Volume | 9 |
| Issue | 5 | Pages | 622-637 |
| PubMed ID | 28264935 | Mgi Jnum | J:264662 |
| Mgi Id | MGI:6161955 | Doi | 10.15252/emmm.201607052 |
| Citation | Ma JF, et al. (2017) STAT3 promotes IFNgamma/TNFalpha-induced muscle wasting in an NF-kappaB-dependent and IL-6-independent manner. EMBO Mol Med 9(5):622-637 |
| abstractText | Cachexia is a debilitating syndrome characterized by involuntary muscle wasting that is triggered at the late stage of many cancers. While the multifactorial nature of this syndrome and the implication of cytokines such as IL-6, IFNgamma, and TNFalpha is well established, we still do not know how various effector pathways collaborate together to trigger muscle atrophy. Here, we show that IFNgamma/TNFalpha promotes the phosphorylation of STAT3 on Y705 residue in the cytoplasm of muscle fibers by activating JAK kinases. Unexpectedly, this effect occurs both in vitro and in vivo independently of IL-6, which is considered as one of the main triggers of STAT3-mediated muscle wasting. pY-STAT3 forms a complex with NF-kappaB that is rapidly imported to the nucleus where it is recruited to the promoter of the iNos gene to activate the iNOS/NO pathway, a well-known downstream effector of IFNgamma/TNFalpha-induced muscle loss. Together, these findings show that STAT3 and NF-kappaB respond to the same upstream signal and cooperate to promote the expression of pro-cachectic genes, the identification of which could provide effective targets to combat this deadly syndrome. |
