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S100A14: A novel negative regulator of cancer stemness and immune evasion by inhibiting STAT3-mediated programmed death-ligand 1 expression in colorectal cancer
DC Field | Value | Language |
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dc.contributor.author | Min, Hye-Young | - |
dc.contributor.author | Cho, Jaebeom | - |
dc.contributor.author | Sim, Jeong Yeon | - |
dc.contributor.author | Boo, Hye-Jin | - |
dc.contributor.author | Lee, Ji-Sun | - |
dc.contributor.author | Lee, Seon-Boon | - |
dc.contributor.author | Lee, Young-Jin | - |
dc.contributor.author | Kim, Sung Joo | - |
dc.contributor.author | Kim, Kyu-Pyo | - |
dc.contributor.author | Park, In-Ja | - |
dc.contributor.author | Hong, Seung-Mo | - |
dc.contributor.author | Zhang, Xue-Li | - |
dc.contributor.author | Zhang, Zhi-Gang | - |
dc.contributor.author | Park, Rang-Woon | - |
dc.contributor.author | Lee, Ho-Young | - |
dc.date.accessioned | 2022-09-30T05:52:14Z | - |
dc.date.available | 2022-09-30T05:52:14Z | - |
dc.date.created | 2022-08-16 | - |
dc.date.issued | 2022-07 | - |
dc.identifier.citation | Clinical and Translational Medicine, Vol.12 No.7, p. e986 | - |
dc.identifier.issn | 2001-1326 | - |
dc.identifier.uri | https://hdl.handle.net/10371/184890 | - |
dc.description.abstract | Background Programmed death-ligand 1 (PD-L1) has functional roles in cancer stem-like cell (CSC) phenotypes and chemoresistance besides immune evasion. Chemotherapy is a common treatment choice for colorectal cancer (CRC) patients; however, chemoresistance limits its effectiveness of treatment. Methods We examined the role of S100A14 (SA14) in CRC by adopting PD-L1(high) subpopulations within CRC cell lines and patient tumours, by establishing PD-L1(high) chemoresistant CRC sublines through prolonged exposure to 5-fluorouracil/oxaliplatin-based chemotherapy in vitro and in vivo, and by analysing a public database. Results We identified a novel function of SA14 as a regulator of immune surveillance, major CSC phenotypes, and survival capacity under hostile microenvironments, including those harbouring chemotherapeutics, and as a prognostic biomarker in CRC. Mechanistically, SA14 inhibits PD-L1 expression by directly interacting with signal transducer and activator of transcription 3 (STAT3) and inducing its proteasome-mediated degradation. While gain-of-SA14 causes loss of PD-L1 expression and tumourigenic potential and sensitisation to chemotherapy-induced apoptosis in chemoresistant CRC cells, loss-of-SA14 causes increases in PD-L1 expression, tumourigenic potential, and chemoresistance in vitro and in vivo. We further show that a combinatorial treatment with chemotherapy and recombinant SA14 protein effectively induces apoptosis in PD-L1(high) chemoresistant CRC cells. Conclusions Our results suggest that SA14-based therapy is an effective strategy to prevent tumour progression and that SA14 is a predictive biomarker for anti-PD-L1 immunotherapy and chemotherapy in combination. | - |
dc.language | 영어 | - |
dc.publisher | Springer Verlag | - |
dc.title | S100A14: A novel negative regulator of cancer stemness and immune evasion by inhibiting STAT3-mediated programmed death-ligand 1 expression in colorectal cancer | - |
dc.type | Article | - |
dc.identifier.doi | 10.1002/ctm2.986 | - |
dc.citation.journaltitle | Clinical and Translational Medicine | - |
dc.identifier.wosid | 000827778200001 | - |
dc.citation.number | 7 | - |
dc.citation.startpage | e986 | - |
dc.citation.volume | 12 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Lee, Ho-Young | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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