beta-catenin/TCF activity regulates IGF-1R tyrosine kinase inhibitor sensitivity in colon cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Hani | - |
dc.contributor.author | Kim, Nayoung | - |
dc.contributor.author | Yoo, Young Ji | - |
dc.contributor.author | Kim, Hyejin | - |
dc.contributor.author | Jeong, Euna | - |
dc.contributor.author | Choi, SeokGyeong | - |
dc.contributor.author | Moon, Sung Un | - |
dc.contributor.author | Oh, Seung Hyun | - |
dc.contributor.author | Mills, Gordon B. | - |
dc.contributor.author | Yoon, Sukjoon | - |
dc.contributor.author | Kim, Woo-Young | - |
dc.date.available | 2020-02-27T08:42:58Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2018-10-04 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3193 | - |
dc.description.abstract | The availability of large-scale drug screening data on cell line panels provides a unique opportunity to identify predictive biomarkers for targeted drug efficacy. Analysis of diverse drug data on similar to 990 cancer cell lines revealed enhanced sensitivity of insulin-like growth factor 1 receptor/Insulin Receptor (IGF-1R/IR) tyrosine kinase inhibitors (TKIs) in colon cancer cells. Interestingly, beta-catenin/TCF(T cell factor)-responsive promoter activity exhibited a significant positive association with IGF-1R/IR TM response, while the mutational status of direct upstream genes, such as CTNNB1 and APC, was not significantly associated with the response. The beta-catenin/TCF activity high cell lines express components of IGF-1R/IR signaling more than the low cell lines explaining their enhanced sensitivity against IGF-1R/IR TKI. Reinforcing beta-catenin/TCF responsive promoter activity by introducing CTNNB1 gain-of-function mutations into IGF-1R/IR TM-resistant cells increased the expression and activity of IGF-1R/IR signaling components and also sensitized the cells to IGF-1R/IR TKIs in vitro and in vivo. Analysis of TCGA data revealed that the stronger beta-catenin/TCF responsive promoter activity was associated with higher IGF-1R and IGF2 transcription in human colon cancer specimens as well. Collectively, compared to the mutational status of upstream genes, beta-catenin/TCF responsive promoter activity has potential to be a stronger predictive positive biomarker for IGF-1R/IR TM responses in colon cancer cells. The present study highlights the potential of transcriptional activity as therapeutic biomarkers for targeted therapies, overcoming the limited ability of upstream genetic mutations to predict responses. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.relation.isPartOf | ONCOGENE | - |
dc.subject | GROWTH-FACTOR-I | - |
dc.subject | RAS SIGNALING PATHWAYS | - |
dc.subject | ADVANCED SOLID TUMORS | - |
dc.subject | COLORECTAL-CANCER | - |
dc.subject | PLASMA-LEVELS | - |
dc.subject | PHASE-I | - |
dc.subject | TRANSCRIPTIONAL ACTIVITY | - |
dc.subject | NUCLEAR-LOCALIZATION | - |
dc.subject | BINDING PROTEIN-3 | - |
dc.subject | INSULIN-RECEPTORS | - |
dc.title | beta-catenin/TCF activity regulates IGF-1R tyrosine kinase inhibitor sensitivity in colon cancer | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000446312900007 | - |
dc.identifier.doi | 10.1038/s41388-018-0362-5 | - |
dc.identifier.bibliographicCitation | ONCOGENE, v.37, no.40, pp.5466 - 5475 | - |
dc.identifier.scopusid | 2-s2.0-85048366358 | - |
dc.citation.endPage | 5475 | - |
dc.citation.startPage | 5466 | - |
dc.citation.title | ONCOGENE | - |
dc.citation.volume | 37 | - |
dc.citation.number | 40 | - |
dc.contributor.affiliatedAuthor | Oh, Seung Hyun | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | GROWTH-FACTOR-I | - |
dc.subject.keywordPlus | RAS SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | ADVANCED SOLID TUMORS | - |
dc.subject.keywordPlus | COLORECTAL-CANCER | - |
dc.subject.keywordPlus | PLASMA-LEVELS | - |
dc.subject.keywordPlus | PHASE-I | - |
dc.subject.keywordPlus | TRANSCRIPTIONAL ACTIVITY | - |
dc.subject.keywordPlus | NUCLEAR-LOCALIZATION | - |
dc.subject.keywordPlus | BINDING PROTEIN-3 | - |
dc.subject.keywordPlus | INSULIN-RECEPTORS | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.