DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Lim, Dae-Sik | - |
dc.contributor.advisor | 임대식 | - |
dc.contributor.advisor | Myung, Seung-Jae | - |
dc.contributor.advisor | 명승재 | - |
dc.contributor.author | Kim, Han Byul | - |
dc.contributor.author | 김한별 | - |
dc.date.accessioned | 2018-05-23T19:36:50Z | - |
dc.date.available | 2018-05-23T19:36:50Z | - |
dc.date.issued | 2017 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=675794&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/241981 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학학제전공, 2017.2,[vi, 83 p. :] | - |
dc.description.abstract | Prostaglandin $E_2 (PGE_2)$ is a key inflammatory mediator governing tissue regeneration, but its chronic activation can also trigger carcinogenesis. Despite its importance, the downstream effectors of $PGE_2$ have remained unclear. Here we show that Yes-associated protein (YAP), a downstream transcriptional co-activator of the Hippo pathway, mediates and amplifies $PGE_2$ function both during tumorigenesis and during regeneration following colitis. $PGE_2$ -induced phosphorylation of CREB transcriptionally activates YAP, which in turn transcriptionally activates cyclooxygenase 2 (COX-2) and EP4, thereby completing a positive feedback loop connecting $PGE_2$ and YAP. Interrupting this loop by YAP gene deletion increases the severity of DSS induced colitis and antagonizes the ability to reverse colitis through manipulations to in-crease colon $PGE_2$ (e.g. genetic ablation of 15-PGDH). Conversely, genetic activation of YAP (by Sav1 gene knockout) synergizes with 15-PGDH gene knock out and in combination induces colon tumors in mice, with tumor development strictly dependent on both intact activity of YAP and of cyclooxygenase. Finally, $PGE_2$ and YAP levels are positively correlated in both sporadic human colon cancers and in human colitis-associated cancers. Our findings thus identify a key role of YAP in amplifying and transducing $PGE_2$ signaling in colon repair and in colon tumorigenesis. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | PGDH | - |
dc.subject | YAP | - |
dc.subject | Colon cancer | - |
dc.subject | NSAID | - |
dc.subject | 프로스트글란딘 E2 | - |
dc.subject | 히포 세포신호전달 | - |
dc.subject | 비스테로이드 항염증제 | - |
dc.subject | 대장암 | - |
dc.subject | 염증성 대장암 | - |
dc.title | Prostaglandin $E_2$ and YAP form a positive feedback loop that promotes colon regeneration and tumorigenesis | - |
dc.title.alternative | $PGE_2$ 와 YAP의 양성 피드백 루프의 의하여 촉진되는 대장 재생 및 대장암 발생에 대한 기능 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학학제전공, | - |
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