EGFR-Tyrosine Kinase Inhibitors Induced Activation of the Autocrine CXCL10/CXCR3 Pathway through Crosstalk between the Tumor and the Microenvironment in EGFR-Mutant Lung Cancer
DC Field | Value | Language |
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dc.contributor.author | Hong, Sook-hee | - |
dc.contributor.author | Kang, Nahyeon | - |
dc.contributor.author | Kim, Okran | - |
dc.contributor.author | Hong, Soon Auck | - |
dc.contributor.author | Park, Juyeon | - |
dc.contributor.author | Kim, Joori | - |
dc.contributor.author | Lee, Myung-Ah | - |
dc.contributor.author | Kang, Jinhyoung | - |
dc.date.accessioned | 2024-01-09T14:35:32Z | - |
dc.date.available | 2024-01-09T14:35:32Z | - |
dc.date.issued | 2023-01 | - |
dc.identifier.issn | 2072-6694 | - |
dc.identifier.issn | 2072-6694 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/70495 | - |
dc.description.abstract | CXCL10 is a cytokine that is elevated during EGFR-TKI treatment in the tumor microenvi-ronment of lung cancer. Here, we report an original study that the impact of the CXCL10/CXCR3 pathway on EGFR-TKI resistance in EGFR-mutant lung cancer through a cytokine array analysis during in vitro coculture with tumor cells and activated PBMCs treated with EGFR-TKI, as well as the serial analysis of CXCL10 in EGFR-mutant lung cancer transgenic mice during EGFR-TKI treatment. In EGFR-mutant tumor cells cocultured with activated PBMCs, EGFR-TKI treatment increased CXCL10 in the supernatant; this activated CXCR3 in the tumor cells to induce the phospho-rylation of Src and the NF-KB subunit, p65, and the expression of HIF-1a. CXCL10 siRNA treatment of EGFR-mutant tumor cells also decreased CXCL10 in the supernatant from coculturing with acti-vated PBMCs, suggesting that the effects of CXCL10 occur via autocrine and paracrine pathways. Importantly, elevated CXCL10/CXCR3 signaling was recapitulated in a transgenic lung cancer mouse model. Our results show that increased CXCL10 levels during early EGFR-TKI treatment stimulate oncogenic signaling of persistent tumor cells to contribute to EGFR-TKI resistance via autocrine and paracrine pathways. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | MDPI | - |
dc.title | EGFR-Tyrosine Kinase Inhibitors Induced Activation of the Autocrine CXCL10/CXCR3 Pathway through Crosstalk between the Tumor and the Microenvironment in EGFR-Mutant Lung Cancer | - |
dc.type | Article | - |
dc.identifier.doi | 10.3390/cancers15010124 | - |
dc.identifier.bibliographicCitation | CANCERS, v.15, no.1 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.wosid | 000911113300001 | - |
dc.identifier.scopusid | 2-s2.0-85146045572 | - |
dc.citation.number | 1 | - |
dc.citation.title | CANCERS | - |
dc.citation.volume | 15 | - |
dc.type.docType | Article | - |
dc.publisher.location | 스위스 | - |
dc.subject.keywordAuthor | EGFR mutation | - |
dc.subject.keywordAuthor | lung cancer | - |
dc.subject.keywordAuthor | EGFR-TKI | - |
dc.subject.keywordAuthor | tyrosine kinase inhibitor | - |
dc.subject.keywordAuthor | CXCL10 | - |
dc.subject.keywordAuthor | CXCR3 | - |
dc.subject.keywordAuthor | NF-kappa B | - |
dc.subject.keywordAuthor | HIF-1 alpha | - |
dc.subject.keywordPlus | GROWTH-FACTOR RECEPTOR | - |
dc.subject.keywordPlus | IFN-GAMMA | - |
dc.subject.keywordPlus | METASTASIS | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | CXCR3 | - |
dc.subject.keywordPlus | HIF-1-ALPHA | - |
dc.subject.keywordPlus | MUTATION | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | SRC | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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