STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner
<p dir="ltr">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, IFNγ, and TNFα is well established, we sti...
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2017
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| _version_ | 1864513557170749440 |
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| author | Jennifer F Ma (18629359) |
| author2 | Brenda J Sanchez (18696940) Derek T Hall (18629356) Anne‐Marie K Tremblay (19691713) Sergio Di Marco (387749) Imed‐Eddine Gallouzi (18629386) |
| author2_role | author author author author author |
| author_facet | Jennifer F Ma (18629359) Brenda J Sanchez (18696940) Derek T Hall (18629356) Anne‐Marie K Tremblay (19691713) Sergio Di Marco (387749) Imed‐Eddine Gallouzi (18629386) |
| author_role | author |
| dc.creator.none.fl_str_mv | Jennifer F Ma (18629359) Brenda J Sanchez (18696940) Derek T Hall (18629356) Anne‐Marie K Tremblay (19691713) Sergio Di Marco (387749) Imed‐Eddine Gallouzi (18629386) |
| dc.date.none.fl_str_mv | 2017-03-06T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.15252/emmm.201607052 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/STAT__3_promotes__IFN____TNF__induced_muscle_wasting_in_an__NF__B_dependent_and__IL__6_independent_manner/27050752 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Oncology and carcinogenesis inflammation iNOS muscle wasting NF-jB STAT3 |
| dc.title.none.fl_str_mv | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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, IFNγ, and TNFα is well established, we still do not know how various effector pathways collaborate together to trigger muscle atrophy. Here, we show that IFNγ/TNFα promotes the phosphorylation of STAT3 on Y705 residue in the cytoplasm of muscle fibers by activating JAK kinases. Unexpectedly, this effect occurs both <i>in vitro</i> and <i>in vivo</i> 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‐κB that is rapidly imported to the nucleus where it is recruited to the promoter of the <i>iN</i><i>os</i> gene to activate the iNOS/NO pathway, a well‐known downstream effector of IFNγ/TNFα‐induced muscle loss. Together, these findings show that STAT3 and NF‐κB 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.</p><h2>Other Information</h2><p dir="ltr">Published in: EMBO Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.15252/emmm.201607052" target="_blank">https://dx.doi.org/10.15252/emmm.201607052</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d6aac7eff8efd398520e9f8e41630985 |
| identifier_str_mv | 10.15252/emmm.201607052 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/27050752 |
| publishDate | 2017 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent mannerJennifer F Ma (18629359)Brenda J Sanchez (18696940)Derek T Hall (18629356)Anne‐Marie K Tremblay (19691713)Sergio Di Marco (387749)Imed‐Eddine Gallouzi (18629386)Biomedical and clinical sciencesImmunologyOncology and carcinogenesisinflammationiNOSmuscle wastingNF-jBSTAT3<p dir="ltr">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, IFNγ, and TNFα is well established, we still do not know how various effector pathways collaborate together to trigger muscle atrophy. Here, we show that IFNγ/TNFα promotes the phosphorylation of STAT3 on Y705 residue in the cytoplasm of muscle fibers by activating JAK kinases. Unexpectedly, this effect occurs both <i>in vitro</i> and <i>in vivo</i> 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‐κB that is rapidly imported to the nucleus where it is recruited to the promoter of the <i>iN</i><i>os</i> gene to activate the iNOS/NO pathway, a well‐known downstream effector of IFNγ/TNFα‐induced muscle loss. Together, these findings show that STAT3 and NF‐κB 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.</p><h2>Other Information</h2><p dir="ltr">Published in: EMBO Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.15252/emmm.201607052" target="_blank">https://dx.doi.org/10.15252/emmm.201607052</a></p>2017-03-06T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.15252/emmm.201607052https://figshare.com/articles/journal_contribution/STAT__3_promotes__IFN____TNF__induced_muscle_wasting_in_an__NF__B_dependent_and__IL__6_independent_manner/27050752CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/270507522017-03-06T03:00:00Z |
| spellingShingle | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner Jennifer F Ma (18629359) Biomedical and clinical sciences Immunology Oncology and carcinogenesis inflammation iNOS muscle wasting NF-jB STAT3 |
| status_str | publishedVersion |
| title | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner |
| title_full | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner |
| title_fullStr | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner |
| title_full_unstemmed | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner |
| title_short | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner |
| title_sort | STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner |
| topic | Biomedical and clinical sciences Immunology Oncology and carcinogenesis inflammation iNOS muscle wasting NF-jB STAT3 |