{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:03:37Z","timestamp":1789153417233,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Institute of Radiological and Medical Sciences (KIRAMS)","award":["50091-2021"],"award-info":[{"award-number":["50091-2021"]}]},{"name":"Korea Institute of Radiological and Medical Sciences (KIRAMS)","award":["NRF-2020R1A2C2005793"],"award-info":[{"award-number":["NRF-2020R1A2C2005793"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["50091-2021"],"award-info":[{"award-number":["50091-2021"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2020R1A2C2005793"],"award-info":[{"award-number":["NRF-2020R1A2C2005793"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Cancer cachexia is a muscle-wasting syndrome that leads to a severely compromised quality of life and increased mortality. A strong association between cachexia and poor prognosis has been demonstrated in intractable cancers, including glioblastoma (GBM). In the present study, it was demonstrated that ionizing radiation (IR), the first-line treatment for GBM, causes cancer cachexia by increasing the exosomal release of plasminogen activator inhibitor-1 (PAI-1) from glioblastoma cells. Exosomal PAI-1 delivered to the skeletal muscle is directly penetrated in the muscles and phosphorylates STAT3 to intensify muscle atrophy by activating muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (Atrogin1); furthermore, it hampers muscle protein synthesis by inhibiting mTOR signaling. Additionally, pharmacological inhibition of PAI-1 by TM5441 inhibited muscle atrophy and rescued muscle protein synthesis, thereby providing survival benefits in a GBM orthotopic xenograft mouse model. In summary, our data delineated the role of PAI-1 in the induction of GBM cachexia associated with radiotherapy-treated GBM. Our data also indicated that targeting PAI-1 could serve as an attractive strategy for the management of GBM following radiotherapy, which would lead to a considerable improvement in the quality of life of GBM patients undergoing radiotherapy.<\/jats:p>","DOI":"10.3390\/cells11193102","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"3102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Exosomal Plasminogen Activator Inhibitor-1 Induces Ionizing Radiation-Adaptive Glioblastoma Cachexia"],"prefix":"10.3390","volume":"11","author":[{"given":"Eunguk","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunkoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haksoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungmin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewan","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3530-5587","authenticated-orcid":false,"given":"Kimoon","family":"Seong","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Dosimetry, National Radiation Emergency Medical Center (NREMC), Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0919-094X","authenticated-orcid":false,"given":"Hyesook","family":"Youn","sequence":"additional","affiliation":[{"name":"Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buhyun","family":"Youn","sequence":"additional","affiliation":[{"name":"Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea"},{"name":"Department of Biological Sciences, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. 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