{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:37:38Z","timestamp":1787229458620,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":12,"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":["81872197"],"award-info":[{"award-number":["81872197"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018540","name":"Natural Science Foundation of Guangdong Province for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["2016A030306003"],"award-info":[{"award-number":["2016A030306003"]}],"id":[{"id":"10.13039\/501100018540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tumour repopulation initiated by residual tumour cells in response to cytotoxic therapy has been described clinically and biologically, but the mechanisms are unclear. Here, we aimed to investigate the mechanisms for the tumour\u2010promoting effect in dying cells and for tumour repopulation in surviving tongue cancer cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tumour repopulation in vitro and in vivo was represented by luciferase activities. The differentially expressed cytokines in the conditioned medium (CM) were identified using a cytokine array. Gain or loss of function was investigated using inhibitors, neutralising antibodies, shRNAs and ectopic overexpression strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that dying tumour cells undergoing cytotoxic therapy increase the growth of living tongue cancer cells in vitro and in vivo. Dying tumour cells create amphiregulin (AREG)\u2010 and basic\u00a0fibroblast growth factor (bFGF)\u2010based extracellular environments via cytotoxic treatment\u2010induced endoplasmic reticulum stress. This environment stimulates growth by activating lysine acetyltransferase 6B (KAT6B)\u2010dependent nuclear factor\u2010kappa B (NF\u2010\u03baB) signalling in living tumour cells. As direct targets of NF\u2010\u03baB, miR\u201022 targets KAT6B to repress its expression, but long noncoding RNAs (lncRNAs) (XLOC_003973 and XLOC_010383) counter the effect of miR\u201022 to enhance KAT6B expression. Moreover, we detected increased AREG and bFGF protein levels in the blood of tongue cancer patients with X\u2010box binding protein\u20101 (XBP1) activation in tumours under cytotoxic therapy and found that XBP1 activation is associated with poor prognosis of patients. We also detected activation of miR\u201022\/lncRNA\/KAT6B\/NF\u2010\u03baB signalling in recurrent cancers compared to paired primary tongue cancers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified the molecular mechanisms of cell death\u2010induced tumour repopulation in tongue cancer. Such insights provide new avenues to identify predictive biomarkers and effective strategies to address cancer progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1166","type":"journal-article","created":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T04:43:13Z","timestamp":1673671393000},"source":"Crossref","is-referenced-by-count":8,"title":["XBP1\u2010elicited environment by chemotherapy potentiates repopulation of tongue cancer cells by enhancing miR\u201022\/lncRNA\/KAT6B\u2010dependent NF\u2010\u03baB signalling"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9964-3801","authenticated-orcid":false,"given":"Xiaoting","family":"Jia","sequence":"first","affiliation":[{"name":"Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation The State Key Laboratory of Respiratory  Guangzhou Guangdong 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