{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:40:12Z","timestamp":1765878012929,"version":"3.48.0"},"reference-count":33,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":24,"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":["81960127"],"award-info":[{"award-number":["81960127"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Pancreatic cancer (PC) is one of the common malignant tumors in gastrointestinal tract. The roles of CERKL in PC are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, online databases were used to analyze CERKL mRNA expression and mutation in PC, predict E3 ligase for CERKL. The roles of CERKL were investigated in cells, mice, and clinic samples. The regulations on CERKL by E3 and lipids fluctuations induced by CERKL were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>It was found that the expression levels of CERKL mRNA and protein were significantly increased in PC. Meanwhile, CERKL promoted PC cells migration and invasion in\u00a0vitro and in\u00a0vivo. L296V mutation on CERKL in PC patient was found in cosmic database. Compared with CERKL, CERKL\u2010L296V could further promote PC cells migration and invasion. Bioinformatics analysis revealed the negative correlation between E3 TRIM21 and CERKL. Furthermore, Trim21 was validated to negatively regulate and bind to CERKL protein. L296V mutation reduced the interaction between CERKL and Trim21, and the ubiquitination on CERKL. Lipidomic analysis showed CERKL down\u2010regulation could increase phosphatidylinositol amount in PC cells. Phosphatidylinositol addition reversed the effects of CERKL in PC cells. Moreover, CERKL knocked down increased phosphatidylinositol 3\u2010phosphate (PI3P) content and autophagy. When CERKL was overexpressed, PI3P and autophagy had opposite changes. Of note, CERKL\u2010L296V had a stronger effect than CERKL on PI3P and autophagy. CERKL induced metastasis could be reduced by autophagy inducer. Thus, CERKL promoted the migration and invasion of pancreatic cancer. L296V mutation enhances the tumor\u2010promoting effect of CERKL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TRIM21\/CERKL\/autophagy pathway exists in PC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71402","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:30:43Z","timestamp":1764066643000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CERKL<\/scp>\n                    Reduced\n                    <scp>PI3P<\/scp>\n                    \/Autophagy to Promote Pancreatic Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Wenying","family":"Zeng","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair Affiliated Hospital of Guilin Medical University  Guilin Guangxi People's Republic of China"},{"name":"Department of Hepatobiliary Surgery Affiliated Shaoyang Central Hospital of University of South China  Shaoyang Hunan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinhui","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair Affiliated Hospital of Guilin Medical University  Guilin Guangxi People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanlian","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair Affiliated Hospital of Guilin Medical University  Guilin Guangxi People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Pan","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair Affiliated 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