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Suppression of DYRK1A/B Drives Endoplasmic Reticulum Stress-mediated Autophagic Cell Death Through Metabolic Reprogramming in Colorectal Cancer Cells

DC Field Value Language
dc.contributor.author구민희-
dc.contributor.author김태일-
dc.contributor.author신상준-
dc.contributor.author양재문-
dc.date.accessioned2022-03-11T05:58:17Z-
dc.date.available2022-03-11T05:58:17Z-
dc.date.issued2022-01-
dc.identifier.issn0250-7005-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/187886-
dc.description.abstractBackground/aim: We previously identified KS40008 (4-(3-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)benzene-1,2-diol), a novel inhibitor of dual-specificity tyrosine phosphorylation-regulated kinase family (DYRK) 1A/B, which exhibited high enzymatic activity and cell proliferation-inhibitory effects in colorectal cancer (CRC) cell lines. In the present study, we aimed to elucidate the antitumor mechanisms of KS40008. Materials and methods: To assess the cytotoxicity of KS40008, we utilized a human cell line and organoid model and performed a CCK-8 assay and real-time cell analysis. Mitochondrial function was determined through mitochondrial staining, mito-stress test, and glycolysis test. In addition, we investigated the mechanisms of cancer cell death induced by KS40008 through immunoblotting, real-time quantitative polymerase chain reaction, reactive oxygen species staining, and immunofluorescence staining. Results: KS40008 exhibited significant cytotoxicity in CRC and non-CRC cell lines, and organoid models compared to 5-fluorouracil, a conventional chemotherapeutic drug. Moreover, KS40008-induced inhibition of DYRK1A/B led to mitochondrial dysfunction and endoplasmic reticulum stress, promoting autophagic cancer cell death. Conclusion: KS40008 exerts antitumor activity through the inhibition of DYRK1A/B. Here, we demonstrated a mechanism by which KS40008 affects endoplasmic reticulum stress-mediated autophagy through the induction of mitochondrial stress, leading to cytotoxicity in CRC.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherInternational Institute of Anticancer Research-
dc.relation.isPartOfANTICANCER RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis / drug effects-
dc.subject.MESHAutophagic Cell Death / drug effects*-
dc.subject.MESHAutophagy / drug effects-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Proliferation / drug effects-
dc.subject.MESHCellular Reprogramming / genetics-
dc.subject.MESHColorectal Neoplasms / drug therapy*-
dc.subject.MESHColorectal Neoplasms / genetics-
dc.subject.MESHColorectal Neoplasms / pathology-
dc.subject.MESHEndoplasmic Reticulum / drug effects-
dc.subject.MESHEndoplasmic Reticulum / genetics-
dc.subject.MESHEndoplasmic Reticulum Stress / drug effects*-
dc.subject.MESHEnzyme Inhibitors / pharmacology*-
dc.subject.MESHFluorouracil / pharmacology-
dc.subject.MESHGlycolysis / drug effects-
dc.subject.MESHHumans-
dc.subject.MESHMetabolic Networks and Pathways / drug effects-
dc.subject.MESHMice-
dc.subject.MESHProtein Serine-Threonine Kinases / antagonists & inhibitors-
dc.subject.MESHProtein Serine-Threonine Kinases / genetics*-
dc.subject.MESHProtein-Tyrosine Kinases / antagonists & inhibitors-
dc.subject.MESHProtein-Tyrosine Kinases / genetics*-
dc.subject.MESHReactive Oxygen Species / metabolism-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleSuppression of DYRK1A/B Drives Endoplasmic Reticulum Stress-mediated Autophagic Cell Death Through Metabolic Reprogramming in Colorectal Cancer Cells-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Radiology (영상의학교실)-
dc.contributor.googleauthorJieon Hwang-
dc.contributor.googleauthorAreum Park-
dc.contributor.googleauthorChinwoo Kim-
dc.contributor.googleauthorDanbi Yu-
dc.contributor.googleauthorHyungju Byun-
dc.contributor.googleauthorMinhee Ku-
dc.contributor.googleauthorJaemoon Yang-
dc.contributor.googleauthorTae Il Kim-
dc.contributor.googleauthorKyu-Sung Jeong-
dc.contributor.googleauthorKi Young Kim-
dc.contributor.googleauthorHyuk Lee-
dc.contributor.googleauthorSang Joon Shin-
dc.identifier.doi10.21873/anticanres.15516-
dc.contributor.localIdA00191-
dc.contributor.localIdA01079-
dc.contributor.localIdA02105-
dc.contributor.localIdA02315-
dc.relation.journalcodeJ00188-
dc.identifier.eissn1791-7530-
dc.identifier.pmid34969768-
dc.identifier.urlhttps://ar.iiarjournals.org/content/42/1/589.long-
dc.subject.keywordDYRK1A protein-
dc.subject.keywordDYRK1B protein-
dc.subject.keywordautophagy-
dc.subject.keywordcolorectal cancer-
dc.subject.keywordendoplasmic reticulum stress-
dc.subject.keywordprotein kinases-
dc.contributor.alternativeNameKu, Min Hee-
dc.contributor.affiliatedAuthor구민희-
dc.contributor.affiliatedAuthor김태일-
dc.contributor.affiliatedAuthor신상준-
dc.contributor.affiliatedAuthor양재문-
dc.citation.volume42-
dc.citation.number1-
dc.citation.startPage589-
dc.citation.endPage598-
dc.identifier.bibliographicCitationANTICANCER RESEARCH, Vol.42(1) : 589-598, 2022-01-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers

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