{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:38:21Z","timestamp":1792442301117,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007180","name":"Faculty of Science, Mahidol University","doi-asserted-by":"publisher","award":["BRF1\u2010A11\/2564"],"award-info":[{"award-number":["BRF1\u2010A11\/2564"]}],"id":[{"id":"10.13039\/501100007180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>\n                    Cancer stem cells (CSCs) drive tumor initiation, metastasis, and therapy resistance. The role of cytoplasmic cyclin\u2010dependent kinase inhibitor 1A (CDKN1A, p21) in CSC biology remains unclear. Since cytoplasmic p21 correlated with advanced stage and metastasis in colorectal cancer (CRC) patients, we investigated its causal role in CSC features\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Cytoplasmic p21 increased spheroid formation and CD133 expression in a mechanism partly dependent on AKT activation. Phosphomimetic p21 (p21\n                    <jats:sup>T145D<\/jats:sup>\n                    ) enhanced spheroid growth, CD133, and stemness factors (Oct3\/4, Nanog, Sox2), whereas nuclear p21 (p21\n                    <jats:sup>T145A<\/jats:sup>\n                    ) reduced them. Immunoprecipitation, proximity ligation assays, and\n                    <jats:italic>in silico<\/jats:italic>\n                    modeling demonstrated that cytoplasmic p21 interacts with the NF\u03baB\u2013I\u03baB complex, promoting NF\u03baB release and activation. Consequently, NF\u03baB targets BCL\u2010xL and COX2 were upregulated in p21\n                    <jats:sup>T145D<\/jats:sup>\n                    \u2010 and AKT\n                    <jats:sup>T308D,S473D<\/jats:sup>\n                    CRC cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in a chorioallantoic membrane (CAM) model, supporting their role as downstream effectors of cytoplasmic p21. Our findings uncover a new function of cytoplasmic p21 in regulating CSC properties through NF\u03baB modulation. Screening p21 subcellular localization may stratify CRC patients with high metastatic risk providing a basis for CSC\u2010targeted therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70150","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:31:37Z","timestamp":1762162297000},"page":"1022-1040","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytoplasmic p21 promotes stemness of colon cancer cells via activation of the\n                    <scp>NF\u03baB<\/scp>\n                    pathway"],"prefix":"10.1002","volume":"20","author":[{"given":"Arnatchai","family":"Maiuthed","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Mahidol University  Bangkok Thailand"},{"name":"Centre of Biopharmaceutical Science for Healthy Ageing, Faculty of Pharmacy Mahidol University  Bangkok 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