Enhanced TLR4 Expression on Colon Cancer Cells After Chemotherapy Promotes Cell Survival and Epithelial-Mesenchymal Transition Through Phosphorylation of GSK3β
DC Field | Value | Language |
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dc.contributor.author | Chung, Yoon Hee | - |
dc.contributor.author | Kim, Daejin | - |
dc.date.available | 2019-03-08T12:40:42Z | - |
dc.date.issued | 2016-07 | - |
dc.identifier.issn | 0250-7005 | - |
dc.identifier.issn | 1791-7530 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/6768 | - |
dc.description.abstract | Background: Phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) by phosphatidyl-inositide 3-kinase (PI3K)/protein kinase B (AKT) or inhibition of GSK3 beta with small-molecule inhibitor attenuates cell survival and proliferation and increases apoptosis in most cancer cell lines. In this study, we investigated the role of phosphorylated GSK3 beta activated by enhanced toll-like receptor 4 (TLR4) expression in drug-treated colon cancer cells as a model of post-chemotherapy cancer cells. Materials and Methods: The effect of TLR4 stimulation on metastasis and apoptosis in drug-exposed colon cancer cells was determined by real-time polymerase chain reaction (PCR) and immunoblotting. Results: Despite the induction of apoptosis after treatment with oxaliplatin and 5-fluorouracil, lipopolysaccharide (LPS) stimulation via increased TLR4 in drug-treated cancer cells effectively inhibited apoptosis through up-regulation of expression of anti-apoptosis-related B-cell lymphoma 2 (BCL2) family proteins [X-linked inhibitor of apoptosis protein (XIAP), BCL2, and survivin] and drug-resistance proteins [multidrug-resistance protein 1 (MDR1), multidrug resistance-associated protein (MRP) 1/2/3]. LPS-mediated signaling in drug-treated cancer cells elevated the expression of phosphorylated GSK3 beta, extracellular signal-regulated kinase (ERK), and the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kappa B). Pharmacological inhibition of GSK3 beta (using SB216763) reduced phosphorylation of GSK3 beta, re-activated caspase-dependent apoptosis, and blocked the expression of cancer stem cell markers and invasive characteristics in LPS-stimulated drug-treated cells. In addition, the ERK-specific inhibitor, PD98059, triggered the apoptosis of TLR4-activated drug-exposed colon cancer cells, whereas there was no effect on the expression of epithelial-mesenchymal transition markers or GSK3 beta phosphorylation. Conclusion: These results suggest that TLR4-induced GSK3 beta and ERK phosphorylation independently controls cancer cell survival and regulation of GSK3 beta and ERK after chemotherapy, making TLR4 a critical target for reducing drug resistance and metastasis in patients with colon cancer. | - |
dc.format.extent | 12 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | INT INST ANTICANCER RESEARCH | - |
dc.title | Enhanced TLR4 Expression on Colon Cancer Cells After Chemotherapy Promotes Cell Survival and Epithelial-Mesenchymal Transition Through Phosphorylation of GSK3β | - |
dc.type | Article | - |
dc.identifier.bibliographicCitation | ANTICANCER RESEARCH, v.36, no.7, pp 3383 - 3394 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000378867600019 | - |
dc.identifier.scopusid | 2-s2.0-84992070829 | - |
dc.citation.endPage | 3394 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 3383 | - |
dc.citation.title | ANTICANCER RESEARCH | - |
dc.citation.volume | 36 | - |
dc.type.docType | Article | - |
dc.publisher.location | 그리이스 | - |
dc.subject.keywordAuthor | TLR4 | - |
dc.subject.keywordAuthor | epithelial-mesenchymal transition | - |
dc.subject.keywordAuthor | EMT | - |
dc.subject.keywordAuthor | GSK3 beta | - |
dc.subject.keywordAuthor | colorectal cancer | - |
dc.subject.keywordPlus | GLYCOGEN-SYNTHASE KINASE-3-BETA | - |
dc.subject.keywordPlus | COLORECTAL-CANCER | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | PANCREATIC-CANCER | - |
dc.subject.keywordPlus | POOR-PROGNOSIS | - |
dc.subject.keywordPlus | KINASE 3 | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | INVASION | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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