{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:31:45Z","timestamp":1788262305058,"version":"build-2803163510"},"reference-count":57,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"1","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Shanghai Sailing Program","award":["20YF1409200"],"award-info":[{"award-number":["20YF1409200"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002545"],"award-info":[{"award-number":["82002545"]}],"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":["81902875"],"award-info":[{"award-number":["81902875"]}],"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":["81972213"],"award-info":[{"award-number":["81972213"]}],"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":["82372874"],"award-info":[{"award-number":["82372874"]}],"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":["81902430"],"award-info":[{"award-number":["81902430"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Commun"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Although the constitutively activated Wnt\/\u03b2\u2010catenin signaling pathway plays vital roles in gastric cancer (GC) progression, few Wnt inhibitors are approved for clinical use. Additionally, the clinical significance of long non\u2010coding RNAs (lncRNAs) in GC intraperitoneal dissemination (IPD) remains elusive. Here, we investigated the function and therapeutic potential of Wnt\u2010transactivated lncRNA, colon cancer\u2010associated transcript 5 (CCAT5), in GC metastasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">LncRNA\u2010sequencing assay was performed to document abundance changes of lncRNAs induced by Wnt family member 3A (Wnt3a) and degradation\u2010resistant \u03b2\u2010catenin (S33Y mutated) in ascites\u2010derived GC cells with low Wnt activity. Luciferase reporter, Chromatin immunoprecipitation (ChIP)\u2010re\u2010ChIP assays were performed to determine how CCAT5 was transcribed. The clinical significance of CCAT5 was examined in 2 cohorts of GC patients. The biological function of CCAT5 was investigated through gain\u2010 and loss\u2010of\u2010function studies. The molecular mechanism was explored through RNA\u2010sequencing, mass spectrometry, and CRISPR\/Cas9\u2010knocknout system. The therapeutic potential of CCAT5 was examined through RNAi\u2010based cell xenograft model and patient\u2010derived xenograft (PDX) model of IPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We identified a novel Wnt\u2010regulated lncRNA, CCAT5, which was transactivated by the \u03b2\u2010catenin\/transcription factor 3 (TCF3) complex. CCAT5 was significantly upregulated in GC and predicted poor prognosis. Functional studies confirmed the promotive role of CCAT5 in GC growth and metastasis. Mechanistically, CCAT5 bound to the C\u2010end domain of signal transducer and activator of transcription 3 (STAT3) and blocks Src homology 2 domain\u2010containing protein tyrosine phosphatase 1 (SHP\u20101)\u2010mediated STAT3\n                      <jats:sup>Y705<\/jats:sup>\n                      dephosphorylation, leading to STAT3 nuclear entry and transactivation, thus accelerating GC progression. Furthermore, we demonstrated that both Wnt3a and \u03b2\u2010catenin acted as activator of STAT3 signaling pathway, and the interplay between CCAT5 and STAT3 was functionally essential for Wnt\u2010drived STAT3 signaling and tumor evolution. Finally, we revealed in vivo si\u2010CCAT5 selectively attenuated growth and metastasis of Wnt\n                      <jats:sup>high<\/jats:sup>\n                      GC, but not Wnt\n                      <jats:sup>low<\/jats:sup>\n                      GC. The combination of si\u2010CCAT5 and oxaliplatin displayed obvious synergistic therapeutic effects on Wnt\n                      <jats:sup>high<\/jats:sup>\n                      PDX mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">We identified a novel Wnt\u2010transactivated lncRNA, CCAT5. Our study revealed a mechanism of STAT3 signaling regulation via canonical Wnt signaling and the functional significance of CCAT5 as critical mediator. We provided conceptual advance that lncRNAs serve as therapeutic targets reversing GC progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cac2.12507","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T19:55:09Z","timestamp":1701114909000},"page":"76-100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["LncRNA\u2010CCAT5\u2010mediated crosstalk between Wnt\/\u03b2\u2010Catenin and STAT3 signaling suggests novel therapeutic approaches for metastatic gastric cancer with high Wnt activity"],"prefix":"10.34133","volume":"44","author":[{"given":"Chenchen","family":"Liu","sequence":"first","affiliation":[{"name":"Fudan University Shanghai Cancer Center","place":["Shanghai, P. R. China"]},{"name":"Shanghai Medical College, Fudan University","place":["Shanghai, P. R. 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Medical College, Fudan University","place":["Shanghai, P. R. China"]},{"name":"Fudan University Shanghai Cancer Center","place":["Shanghai, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6292-317X","authenticated-orcid":false,"given":"Yanong","family":"Wang","sequence":"additional","affiliation":[{"name":"Fudan University Shanghai Cancer Center","place":["Shanghai, P. R. China"]},{"name":"Shanghai Medical College, Fudan University","place":["Shanghai, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Liu","sequence":"additional","affiliation":[{"name":"Fudan University Shanghai Cancer Center","place":["Shanghai, P. R. China"]},{"name":"Shanghai Medical College, Fudan University","place":["Shanghai, P. R. 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Cancer Commun (Lond). 2021;41((10)):1037\u20101048.","journal-title":"Cancer Commun (Lond)."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.21037\/tgh.2019.08.03","article-title":"Surgical management of metastatic gastric cancer: moving beyond the guidelines","volume":"4","author":"Guner A","year":"2019","unstructured":"Guner A, Yildirim R. Surgical management of metastatic gastric cancer: moving beyond the guidelines. Transl Gastroenterol Hepatol. 2019;4:58.","journal-title":"Transl Gastroenterol Hepatol."},{"issue":"2","key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.5230\/jgc.2020.20.e15","article-title":"Recent Advances in Intra\u2010peritoneal Chemotherapy for Gastric Cancer","volume":"20","author":"Chia DKA","year":"2020","unstructured":"Chia DKA, So JBY. Recent Advances in Intra\u2010peritoneal Chemotherapy for Gastric Cancer. 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