Cited 15 times in
HER2 Regulates Cancer Stem Cell Activities via the Wnt Signaling Pathway in Gastric Cancer Cells
DC Field | Value | Language |
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dc.contributor.author | 김지현 | - |
dc.contributor.author | 정다현 | - |
dc.contributor.author | 정희철 | - |
dc.date.accessioned | 2019-12-18T01:11:25Z | - |
dc.date.available | 2019-12-18T01:11:25Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 0030-2414 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/173410 | - |
dc.description.abstract | INTRODUCTION: Human epidermal growth factor 2 (HER2) gene overexpression in breast carcinoma cell lines has been shown to drive mammary carcinogenesis and tumor growth and invasion through its effects on mammary stem cells. OBJECTIVE: Therefore, we investigated the mechanism by which HER2 regulates cancer stem cell (CSC) activity in gastric cancer cells. METHODS: HER2 was transfected into MKN28 gastric cancer cells, and its role in regulating CSC activity was determined by characterizing the HER2-overexpressing cells. RESULTS: The sphere formation assay revealed that the sphere sizes and frequency of sphere formation were significantly greater for the HER2-overexpressing cells than for the MKN28 control cells. The CSC markers Oct-4 and BMI1 were more highly expressed in the HER2-overexpressing cells, as were the EMT markers. This was accompanied by a significant enhancement in cellular invasion of the Matrigel and migration. The E-cadherin level was significantly downregulated, and the mesenchymal marker Snail upregulated, in the HER2-transfected cells. HER2 overexpression activated the well-characterized CSC-associated Wnt/β-catenin signaling pathway, as shown by the luciferase assay. After treatment of these cells with the Wnt signal inhibitor PRI-724, the BMI1 and Oct-4 levels were decreased for 24 h and Snail was also downregulated. Immunofluorescence staining revealed the significant restoration of E-cadherin levels in the HER2-transfected cells after PRI-724 treatment. CONCLUSIONS: These results established a role for HER2 in regulating gastric CSC activity, with Wnt/β-catenin signaling being mediated via a HER2-dependent pathway. In summary, HER2-overexpressing gastric cancer cells exhibited increased stemness and invasiveness and were regulated by Wnt/β-catenin signaling. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Karger | - |
dc.relation.isPartOf | ONCOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Antigens, CD/analysis | - |
dc.subject.MESH | Cadherins/analysis | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Neoplasm Invasiveness | - |
dc.subject.MESH | Neoplastic Stem Cells/physiology* | - |
dc.subject.MESH | Octamer Transcription Factor-3/analysis | - |
dc.subject.MESH | Polycomb Repressive Complex 1/analysis | - |
dc.subject.MESH | Receptor, ErbB-2/analysis | - |
dc.subject.MESH | Receptor, ErbB-2/physiology* | - |
dc.subject.MESH | Stomach Neoplasms/chemistry | - |
dc.subject.MESH | Stomach Neoplasms/pathology* | - |
dc.subject.MESH | Wnt Signaling Pathway/physiology* | - |
dc.subject.MESH | beta Catenin/analysis | - |
dc.title | HER2 Regulates Cancer Stem Cell Activities via the Wnt Signaling Pathway in Gastric Cancer Cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Da Hyun Jung | - |
dc.contributor.googleauthor | Yoo Jin Bae | - |
dc.contributor.googleauthor | Jie-Hyun Kim | - |
dc.contributor.googleauthor | You Keun Shin | - |
dc.contributor.googleauthor | Hei-Cheul Jeung | - |
dc.identifier.doi | 10.1159/000502845 | - |
dc.contributor.localId | A00996 | - |
dc.contributor.localId | A03591 | - |
dc.contributor.localId | A03794 | - |
dc.relation.journalcode | J02416 | - |
dc.identifier.eissn | 1423-0232 | - |
dc.identifier.pmid | 31550723 | - |
dc.identifier.url | https://www.karger.com/Article/FullText/502845 | - |
dc.subject.keyword | Cancer stem cell | - |
dc.subject.keyword | Epithelial-to-mesenchymal transition | - |
dc.subject.keyword | Gastric cancer | - |
dc.subject.keyword | HER2 | - |
dc.subject.keyword | Wnt | - |
dc.contributor.alternativeName | Kim, Jie-Hyun | - |
dc.contributor.affiliatedAuthor | 김지현 | - |
dc.contributor.affiliatedAuthor | 정다현 | - |
dc.contributor.affiliatedAuthor | 정희철 | - |
dc.citation.volume | 97 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 311 | - |
dc.citation.endPage | 318 | - |
dc.identifier.bibliographicCitation | ONCOLOGY, Vol.97(5) : 311-318, 2019 | - |
dc.identifier.rimsid | 63597 | - |
dc.type.rims | ART | - |
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