{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:01:04Z","timestamp":1790319664156,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005925","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["TCMF\u2010CP 115\u201003"],"award-info":[{"award-number":["TCMF\u2010CP 115\u201003"]}],"id":[{"id":"10.13039\/501100005925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sunitinib resistance contributes to poor outcomes in advanced renal cell carcinoma (RCC). This study investigated the anti\u2010metastatic effects and underlying mechanisms of melatonin in sunitinib\u2010resistant (SR)\u2010RCC. Melatonin significantly inhibited the migration and invasion of A498\u2010SR and Caki\u20101\u2010SR cells. SR\u2010RCC cells exhibited elevated CTSD expression, impaired endoplasmic reticulum (ER) stress signaling with reduced GRP78 and IRE1\u03b1, and enhanced p38 MAPK activation, all of which were reversed by melatonin. Silencing p38 MAPK further potentiated the inhibitory effects of melatonin on cell migration and invasion. Mechanistically, CTSD expression was regulated through both GRP78\/p38 MAPK\u2010mediated ER stress.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , melatonin markedly reduced lung metastasis of Caki\u20101\u2010SR cells without causing significant toxicity to major organs. Collectively, these findings demonstrate that melatonin inhibited the metastatic potential of SR\u2010RCC by decreasing CTSD expression, restoring ER stress response, and decreasing p38 MAPK expression, supporting its potential as an anti\u2010metastatic therapeutic agent for SR\u2010RCC\n                  <\/jats:p>","DOI":"10.1111\/jpi.70183","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:06:33Z","timestamp":1789045593000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin Inhibits Metastasis of Sunitinib\u2010Resistant Renal Cell Carcinoma Cells Via the GRP78\/p38\/CTSD Expression"],"prefix":"10.1111","volume":"78","author":[{"given":"Po\u2010Yu","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Chiayi County Taiwan"},{"name":"Institute of 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