Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells
DC Field | Value | Language |
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dc.contributor.author | Jung, M-J | - |
dc.contributor.author | Rho, J-K | - |
dc.contributor.author | Kim, Y-M | - |
dc.contributor.author | Jung, J. E. | - |
dc.contributor.author | Jin, Y. B. | - |
dc.contributor.author | Ko, Y-G | - |
dc.contributor.author | Lee, J-S | - |
dc.contributor.author | Lee, S-J | - |
dc.contributor.author | Lee, J. C. | - |
dc.contributor.author | Park, M-J | - |
dc.date.accessioned | 2021-08-02T18:58:32Z | - |
dc.date.available | 2021-08-02T18:58:32Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2013-01 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/26807 | - |
dc.description.abstract | The hypothesis of cancer stem cells has been proposed to explain the therapeutic failure in a variety of cancers including lung cancers. Previously, we demonstrated acquisition of epithelial-mesenchymal transition, a feature highly reminiscent of cancer stem-like cells, in gefitinib-resistant A549 cells (A549/GR). Here, we show that A549/GR cells contain a high proportion of CXCR4+ cells that are responsible for having high potential of self-renewal activity in vitro and tumorigenicity in vivo. A549/GR cells exhibited strong sphere-forming activity and high CXCR4 expression and SDF-1 alpha secretion compared with parent cells. Pharmacological inhibition (AMD3100) and/or siRNA transfection targeting CXCR4 significantly suppressed sphere-forming activity in A549 and A549/GR cells, and in various non-small cell lung cancer (NSCLC) cell lines. A549/GR cells showed enhanced Akt, mTOR and STAT3 (Y705) phosphorylation. Pharmacological inhibition of phosphatidyl inositol 3-kinase or transfection with wild-type PTEN suppressed phosphorylation of Akt, mTOR and STAT3 (Y705), sphere formation, and CXCR4 expression in A549/GR cells, whereas mutant PTEN enhanced these events. Inhibition of STAT3 by WP1066 or siSTAT3 significantly suppressed the sphere formation, but not CXCR4 expression, indicating that STAT3 is a downstream effector of CXCR4-mediated signaling. FACS-sorted CXCR4+ A549/GR cells formed many large spheres, had self-renewal capacity, demonstrated radiation resistance in vitro and exhibited stronger tumorigenic potential in vivo than CXCR4 cells. Lentiviral-transduction of CXCR4 enhanced sphere formation and tumorigenicity in H460 and A549 cells, whereas introduction of siCXCR4 suppressed these activities in A549/GR cells. Our data indicate that CXCR4 NSCLC cells are strong candidates for tumorigenic stem-like cancer cells that maintain sternness through a CXCR4-medated STAT3 pathway and provide a potential therapeutic target for eliminating these malignant cells in NSCLC. Oncogene (2013) 32, 209-221; doi:10.1038/onc.2012.37; published online 27 February 2012 | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, S-J | - |
dc.identifier.doi | 10.1038/onc.2012.37 | - |
dc.identifier.scopusid | 2-s2.0-84872192934 | - |
dc.identifier.wosid | 000314075500009 | - |
dc.identifier.bibliographicCitation | ONCOGENE, v.32, no.2, pp.209 - 221 | - |
dc.relation.isPartOf | ONCOGENE | - |
dc.citation.title | ONCOGENE | - |
dc.citation.volume | 32 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 209 | - |
dc.citation.endPage | 221 | - |
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 | GROWTH-FACTOR | - |
dc.subject.keywordPlus | CHEMOKINE RECEPTOR-4 | - |
dc.subject.keywordPlus | TUMOR-GROWTH | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | A549 | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | POPULATION | - |
dc.subject.keywordPlus | INVASION | - |
dc.subject.keywordAuthor | non-small cell lung cancer | - |
dc.subject.keywordAuthor | cancer stern cell | - |
dc.subject.keywordAuthor | CXCR4 | - |
dc.subject.keywordAuthor | PI3K/PTEN/Akt/mTOR signaling | - |
dc.subject.keywordAuthor | STAT3 signaling | - |
dc.subject.keywordAuthor | tumorigenicity | - |
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