{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:03:30Z","timestamp":1789153410287,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81988101"],"award-info":[{"award-number":["81988101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81830086"],"award-info":[{"award-number":["81830086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702748"],"award-info":[{"award-number":["81702748"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872398"],"award-info":[{"award-number":["81872398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2016YFA0500303"],"award-info":[{"award-number":["2016YFA0500303"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cachexia, characterized by loss of skeletal muscle mass and function, is estimated to inflict the majority of patients with oesophageal squamous cell carcinoma (ESCC) and associated with their poor prognosis. However, its underlying mechanisms remain elusive. Here, we developed an ESCC\u2010induced cachexia mouse model using human xenograft ESCC cell lines and found that ESCC\u2010derived extracellular vesicles (EVs) containing prolyl 4\u2010hydroxylase subunit beta (P4HB) induced apoptosis of skeletal muscle cells. We further identified that P4HB promoted apoptotic response through activating ubiquitin\u2010dependent proteolytic pathway and regulated the stability of phosphoglycerate dehydrogenase (PHGDH) and subsequent antiapoptotic protein Bcl\u20102. Additionally, we proved that the P4HB inhibitor, CCF642, not only rescued apoptosis of muscle cells in vitro, but also prevented body weight loss and muscle wasting in ESCC\u2010induced cachexia mouse model. Overall, these findings demonstrate a novel pathway for ESCC\u2010induced muscle wasting and advocate for the development of P4HB as a potential intervention target for cachexia in patients with ESCC.<\/jats:p>","DOI":"10.1002\/jev2.12060","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T05:30:22Z","timestamp":1615354222000},"source":"Crossref","is-referenced-by-count":52,"title":["Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH\/Bcl\u20102\/caspase\u20103 pathway"],"prefix":"10.1002","volume":"10","author":[{"given":"Xiaohan","family":"Gao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiren","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangchao","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qimin","family":"Zhan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.10.004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/152308603768295096"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2015.200"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3829"},{"issue":"1","key":"e_1_2_8_6_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer\u2010associated cachexia","volume":"4","author":"Baracos V. E.","year":"2018","journal-title":"Nature Reviews Disease Primers"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108687"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12233"},{"issue":"10","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/0026-0495(95)90040-3","article-title":"Negative impact of cancer chemotherapy on protein metabolism in healthy and tumor\u2010bearing rats","volume":"44","author":"Bricon T. L.","year":"1995","journal-title":"Metabolism"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/dote\/dox016"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.12.013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20180213"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3169"},{"issue":"2","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cyto.2010.05.006","article-title":"Circulating leptin and inflammatory response in esophageal cancer, esophageal cancer\u2010related cachexia\u2010anorexia syndrome (CAS) and non\u2010malignant CAS of the alimentary tract","volume":"51","author":"Diakowska D.","year":"2010","journal-title":"Cytokine"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/317267a0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4093"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2006.06.001"},{"issue":"22","key":"e_1_2_8_19_1","first-page":"8085","article-title":"Beta\u2010catenin expression is altered in human colonic aberrant crypt foci","volume":"61","author":"Hao X. P.","year":"2001","journal-title":"Cancer Research"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1402714111"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.467"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2015.1017690"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.05.032"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.2308"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12528"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2017.00069"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.09.005"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.616359"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2753"},{"issue":"5","key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"e2818","DOI":"10.1038\/cddis.2017.213","article-title":"Protein disulfide isomerase\u2010mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis","volume":"8","author":"Ping S","year":"2017","journal-title":"Cell Death Discovery"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308350"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-6020-5_11"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1995.0312e.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13176"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3410\/B3-15"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1535750"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-3099"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071028"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.16.7467"},{"issue":"7635","key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nature20784","article-title":"Epigenome\u2010wide association study of body mass index, and the adverse outcomes of adiposity","volume":"541","author":"Wahl S.","year":"2016","journal-title":"Nature"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14337"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.84"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.10.026"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00726-x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2005.07.016"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i22.2381"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.15"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12060","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jev2.12060","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T15:15:51Z","timestamp":1760627751000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jev2.12060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1002\/jev2.12060"],"URL":"https:\/\/doi.org\/10.1002\/jev2.12060","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3]]},"article-number":"e12060"}}