Cited 15 times in
Downregulated CLIP3 induces radioresistance by enhancing stemness and glycolytic flux in glioblastoma
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 강석구 | - |
dc.date.accessioned | 2021-10-21T00:13:41Z | - |
dc.date.available | 2021-10-21T00:13:41Z | - |
dc.date.issued | 2021-09 | - |
dc.identifier.issn | 0392-9078 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/185429 | - |
dc.description.abstract | Background: Glioblastoma Multiforme (GBM) is a malignant primary brain tumor in which the standard treatment, ionizing radiation (IR), achieves a median survival of about 15 months. GBM harbors glioblastoma stem-like cells (GSCs), which play a crucial role in therapeutic resistance and recurrence. Methods: Patient-derived GSCs, GBM cell lines, intracranial GBM xenografts, and GBM sections were used to measure mRNA and protein expression and determine the related molecular mechanisms by qRT-PCR, immunoblot, immunoprecipitation, immunofluorescence, OCR, ECAR, live-cell imaging, and immunohistochemistry. Orthotopic GBM xenograft models were applied to investigate tumor inhibitory effects of glimepiride combined with radiotherapy. Results: We report that GSCs that survive standard treatment radiation upregulate Speedy/RINGO cell cycle regulator family member A (Spy1) and downregulate CAP-Gly domain containing linker protein 3 (CLIP3, also known as CLIPR-59). We discovered that Spy1 activation and CLIP3 inhibition coordinately shift GBM cell glucose metabolism to favor glycolysis via two cellular processes: transcriptional regulation of CLIP3 and facilitating Glucose transporter 3 (GLUT3) trafficking to cellular membranes in GBM cells. Importantly, in combination with IR, glimepiride, an FDA-approved medication used to treat type 2 diabetes mellitus, disrupts GSCs maintenance and suppresses glycolytic activity by restoring CLIP3 function. In addition, combining radiotherapy and glimepiride significantly reduced GBM growth and improved survival in a GBM orthotopic xenograft mouse model. Conclusions: Our data suggest that radioresistant GBM cells exhibit enhanced stemness and glycolytic activity mediated by the Spy1-CLIP3 axis. Thus, glimepiride could be an attractive strategy for overcoming radioresistance and recurrence by rescuing CLIP3 expression. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | BioMed Central | - |
dc.relation.isPartOf | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Downregulated CLIP3 induces radioresistance by enhancing stemness and glycolytic flux in glioblastoma | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Neurosurgery (신경외과학교실) | - |
dc.contributor.googleauthor | Hyunkoo Kang | - |
dc.contributor.googleauthor | Sungmin Lee | - |
dc.contributor.googleauthor | Kyeongmin Kim | - |
dc.contributor.googleauthor | Jaewan Jeon | - |
dc.contributor.googleauthor | Seok-Gu Kang | - |
dc.contributor.googleauthor | HyeSook Youn | - |
dc.contributor.googleauthor | Hae Yu Kim | - |
dc.contributor.googleauthor | BuHyun Youn | - |
dc.identifier.doi | 10.1186/s13046-021-02077-4 | - |
dc.contributor.localId | A00036 | - |
dc.relation.journalcode | J03807 | - |
dc.identifier.eissn | 1756-9966 | - |
dc.identifier.pmid | 34488821 | - |
dc.subject.keyword | CLIP3 | - |
dc.subject.keyword | Glimepiride | - |
dc.subject.keyword | Glioblastoma | - |
dc.subject.keyword | Glioblastoma stem-like cells | - |
dc.subject.keyword | Radioresistance | - |
dc.contributor.alternativeName | Kang, Seok Gu | - |
dc.contributor.affiliatedAuthor | 강석구 | - |
dc.citation.volume | 40 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 282 | - |
dc.identifier.bibliographicCitation | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, Vol.40(1) : 282, 2021-09 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.