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Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition

DC FieldValueLanguage
dc.contributor.author고윤우-
dc.contributor.author기현정-
dc.contributor.author양재문-
dc.date.accessioned2019-02-12T16:49:07Z-
dc.date.available2019-02-12T16:49:07Z-
dc.date.issued2018-
dc.identifier.issn1347-9032-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/167159-
dc.description.abstractRecurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherWiley Publishing on behalf of the Japanese Cancer Association-
dc.relation.isPartOfCANCER SCIENCE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleFibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Otorhinolaryngology (이비인후과학교실)-
dc.contributor.googleauthorMyung Jin Ban-
dc.contributor.googleauthorHyung Kwon Byeon-
dc.contributor.googleauthorYeon Ju Yang-
dc.contributor.googleauthorSojung An-
dc.contributor.googleauthorJae Wook Kim-
dc.contributor.googleauthorJi‐Hoon Kim-
dc.contributor.googleauthorDa Hee Kim-
dc.contributor.googleauthorJaemoon Yang-
dc.contributor.googleauthorHyunjung Kee-
dc.contributor.googleauthorYoon Woo Koh-
dc.identifier.doi10.1111/cas.13839-
dc.contributor.localIdA00133-
dc.contributor.localIdA00279-
dc.contributor.localIdA00279-
dc.contributor.localIdA02315-
dc.contributor.localIdA02315-
dc.relation.journalcodeJ00454-
dc.identifier.eissn1349-7006-
dc.identifier.pmid30343534-
dc.subject.keywordMAP kinase signaling system-
dc.subject.keywordMEK inhibition-
dc.subject.keywordfibroblast growth factor receptor-
dc.subject.keywordhead and neck cancer-
dc.subject.keywordreceptor cross-talk-
dc.contributor.alternativeNameKho, Yoon Woo-
dc.contributor.affiliatedAuthor고윤우-
dc.contributor.affiliatedAuthor기현정-
dc.contributor.affiliatedAuthor기현정-
dc.contributor.affiliatedAuthor양재문-
dc.contributor.affiliatedAuthor양재문-
dc.citation.volume109-
dc.citation.number12-
dc.citation.startPage3816-
dc.citation.endPage3825-
dc.identifier.bibliographicCitationCANCER SCIENCE, Vol.109(12) : 3816-3825, 2018-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers

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