(The) role of KIF3A in the regulation of Wnt signaling in non-small cell lung cancer비소세포 폐암에서의 KIF3A에 의한 Wnt 신호전달 조절 연구

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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.
Advisors
Kim, Joonresearcher김준researcherJang, Se jinresearcher장세진researcher
Description
한국과학기술원 :의과학학제전공,
Publisher
한국과학기술원
Issue Date
2016
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 의과학학제전공, 2016.8 ,[vi, 99 p. :]

Keywords

KIF3A; Wnt/$\beta-catenin$ signaling; Non-small-cell lung cancer; Primary cilia; Wnt/$\beta-catenin$ 신호전달체계; β-arrestin; 비소세포폐암; 원발성 섬모

URI
http://hdl.handle.net/10203/222267
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=663162&flag=dissertation
Appears in Collection
MSE-Theses_Ph.D.(박사논문)
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