{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:30:51Z","timestamp":1785803451825,"version":"3.56.0"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive metastasis and poor response to chemotherapy, largely driven by epithelial\u2013mesenchymal transition (EMT) and chemokine signaling. Cannabidiol (CBD), a non\u2010psychoactive phytocannabinoid, has shown anticancer potential, yet its mechanisms in EMT regulation remain underexplored in PDAC. In this study, we demonstrate that CBD significantly suppresses the expression of CXCR4\/CXCR7 and matrix metalloproteinases (MMP\u20102\/9), leading to reduced migration and invasion of MIA PaCa\u20102, PANC\u20101, and AsPC\u20101 cells. Moreover, CBD reversed CXCL12\u2010induced EMT by downregulating mesenchymal markers and restoring epithelial markers. Mechanistically, CBD inhibited the expression of the long non\u2010coding RNA <jats:italic>MALAT1<\/jats:italic>, a known EMT regulator, and antagonized its pro\u2010invasive effects. Overexpression of <jats:italic>MALAT1<\/jats:italic> activated the PI3K\/Akt\/mTOR pathway and enhanced EMT\u2010related protein expression, all of which were effectively reversed by CBD. Furthermore, the combination of CBD and gemcitabine exhibited synergistic inhibition of <jats:italic>MALAT1<\/jats:italic>, EMT markers, and PI3K\/Akt\/mTOR signaling without inducing cytotoxicity, suggesting a therapeutic advantage. Collectively, these findings reveal a novel mechanism through which CBD impedes PDAC metastasis and underscore its promise as a complementary agent in chemotherapy regimens.<\/jats:p>","DOI":"10.1002\/iub.70042","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T10:27:13Z","timestamp":1754476033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cannabidiol Suppresses <scp>EMT<\/scp> in Pancreatic Cancer via Inhibition of <i>MALAT1<\/i><scp>lncRNA<\/scp> and <scp>PI3K\/Akt\/mTOR<\/scp> Signaling Pathway"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-8085","authenticated-orcid":false,"given":"Na Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Science in Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Yun","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Young","family":"Um","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine Kyung Hee University  Seoul Republic of Korea"},{"name":"Kyung Hee Institute of Convergence Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-0612","authenticated-orcid":false,"given":"Kwang Seok","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine Kyung Hee University  Seoul Republic of Korea"},{"name":"Kyung Hee Institute of Convergence Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.05.027"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2018.01.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02050.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04298.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.110995"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.08.033"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12020320"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-013-1028-y"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.02.001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncrna.2024.08.002"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12051245"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02540-y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0008"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-01965-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S276022"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110433"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2022.05.018"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121458"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12070891"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10101406"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2329"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.015"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.028"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3049"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3727\/096504016X14549667334007"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-023-00467-8"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S136878"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16010234"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21070965"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041230"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011923"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.3829"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.16199"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2819"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4138"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-22-907"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1004212"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2025.01.003"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02998-6"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00828-5"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01827-6"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12631"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186740"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17121644"},{"key":"e_1_2_8_48_1","first-page":"2016","article-title":"Combined Gene Expression Analysis of Whole\u2010Tissue and Microdissected Pancreatic Ductal Adenocarcinoma Identifies Genes Specifically Overexpressed in Tumor Epithelia","volume":"55","author":"Badea L.","year":"2008","journal-title":"Hepato\u2010Gastroenterology"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0209"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.07.007"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.70042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T08:54:15Z","timestamp":1756284855000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.70042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/iub.70042"],"URL":"https:\/\/doi.org\/10.1002\/iub.70042","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70042"}}