DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Joon | - |
dc.contributor.advisor | 김준 | - |
dc.contributor.advisor | Jang, Se jin | - |
dc.contributor.advisor | 장세진 | - |
dc.contributor.author | Kim, Minsuh | - |
dc.contributor.author | 김민서 | - |
dc.date.accessioned | 2017-03-29T02:47:22Z | - |
dc.date.available | 2017-03-29T02:47:22Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=663162&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/222267 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학학제전공, 2016.8 ,[vi, 99 p. :] | - |
dc.description.abstract | Aberrant $Wnt/ \beta -catenin$ signaling is implicated in the progression of several human cancers, including non-small-cell lung cancer (NSCLC). However, mutations in $Wnt/ \beta -catenin$ pathway components are uncommon in NSCLC, and epigenetic mechanisms controlling the Wnt/β-catenin pathway remain unclear. Here, we show that KIF3A, a member of the kinesin-2 motor family, plays a key role in suppressing $Wnt/ \beta -catenin$ signaling in NSCLC cells. Knockdown of KIF3A increases both $\beta -catenin$ levels and transcriptional activity, with a concomitant promotion of malignant phenotypes, such as enhanced proliferation and migration, and upregulation of stemness markers. KIF3A binds to $\beta -arrestin$, and KIF3A depletion allows $\beta -arrestin$ to form a complex with DVL2 and AXIN, resulting in $\beta -catenin$ stabilization. Although primary cilia, of which the biogenesis requires KIF3A, are thought to restrain the Wnt response, pharmacological inhibi-tion of ciliogenesis does not enhance $\beta -catenin$ activity in NSCLC cells. A correlation between KIF3A loss and worse NSCLC prognosis as well as upregulation of $\beta -catenin$ and Cyclin D1 further suggests that KIF3A is a suppressor of $Wnt/\beta -catenin$ signaling and tumorigenesis in NSCLC. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | KIF3A | - |
dc.subject | Wnt/$\beta-catenin$ signaling | - |
dc.subject | Non-small-cell lung cancer | - |
dc.subject | Primary cilia | - |
dc.subject | Wnt/$\beta-catenin$ 신호전달체계 | - |
dc.subject | β-arrestin | - |
dc.subject | 비소세포폐암 | - |
dc.subject | 원발성 섬모 | - |
dc.title | (The) role of KIF3A in the regulation of Wnt signaling in non-small cell lung cancer | - |
dc.title.alternative | 비소세포 폐암에서의 KIF3A에 의한 Wnt 신호전달 조절 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학학제전공, | - |
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