Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1 alpha mediated by the PTEN/PI3K/Akt pathway
DC Field | Value | Language |
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dc.contributor.author | Park, J-H | - |
dc.contributor.author | Lee, J-Y | - |
dc.contributor.author | Shin, D-H | - |
dc.contributor.author | Jang, K-S | - |
dc.contributor.author | Kim, H-J | - |
dc.contributor.author | Kong, Gu | - |
dc.date.accessioned | 2022-07-16T18:24:52Z | - |
dc.date.available | 2022-07-16T18:24:52Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2011-11 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/167259 | - |
dc.description.abstract | Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and found that Mel-18 was a novel regulator of HIF-1 alpha. Mel-18 negatively regulated the HIF-1 alpha expression and its target gene VEGF transcription during both normoxia and hypoxia. We demonstrated that Mel-18 regulated the HIF-1 alpha expression and activity via the PI3K/Akt pathway. Loss of Mel-18 downregulated Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression, consequently activating the PI3K/Akt/MDM2 pathway, and leading to an increase of HIF-1 alpha protein level. Mel-18 modulated the HIF-1 alpha transcriptional activity via regulating the cytoplasmic retention of FOXO3a, a downstream effector of Akt, and recruitment of HIF-1 alpha/CBP complex to the VEGF promoter. Furthermore, our data shows that Mel-18 blocked tumor angiogenesis both in vitro and in vivo. Mel-18 overexpression inhibited in vitro tube formation in human umbilical endothelial cells (HUVECs). Xenografts in NOD/SCID mice derived from stably Mel-18 knocked down MCF7 human breast cancer cells showed increased tumor volume, microvessel density, and phospho-Akt and HIF-1a expression levels. In conclusion, our findings provide that Mel-18 is a novel regulator of tumor angiogenesis through regulating HIF-1 alpha and its target VEGF expressions mediated by the PTEN/PI3K/Akt pathway, suggesting a new tumor-suppressive role of Mel-18 in human breast cancer. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1 alpha mediated by the PTEN/PI3K/Akt pathway | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jang, K-S | - |
dc.contributor.affiliatedAuthor | Kong, Gu | - |
dc.identifier.doi | 10.1038/onc.2011.174 | - |
dc.identifier.scopusid | 2-s2.0-80755140181 | - |
dc.identifier.wosid | 000296890700005 | - |
dc.identifier.bibliographicCitation | ONCOGENE, v.30, no.45, pp.4578 - 4589 | - |
dc.relation.isPartOf | ONCOGENE | - |
dc.citation.title | ONCOGENE | - |
dc.citation.volume | 30 | - |
dc.citation.number | 45 | - |
dc.citation.startPage | 4578 | - |
dc.citation.endPage | 4589 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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.subject.keywordPlus | INDUCIBLE FACTOR 1-ALPHA | - |
dc.subject.keywordPlus | FORKHEAD TRANSCRIPTION FACTOR | - |
dc.subject.keywordPlus | REGULATES CELL-PROLIFERATION | - |
dc.subject.keywordPlus | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | SUPPRESSOR PROTEIN | - |
dc.subject.keywordPlus | UBIQUITIN LIGASE | - |
dc.subject.keywordPlus | VEGF EXPRESSION | - |
dc.subject.keywordPlus | POOR-PROGNOSIS | - |
dc.subject.keywordPlus | HYPOXIA | - |
dc.subject.keywordAuthor | Mel-18 | - |
dc.subject.keywordAuthor | polycomb group proteins | - |
dc.subject.keywordAuthor | Akt | - |
dc.subject.keywordAuthor | angiogenesis | - |
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