연구논문

세부과제번호 2013M3A9D5072550 단계 1단계 3차년도
세부과제명 마우스 운동 및 대사표현형 분석 기반 구축 및 서비스 제공 공동 유/무 N
SCI여부 Y 게재년월 2016-08
논문제목 Ninjurin1 inhibits colitis-mediated colon cancer development and growth by suppression of macrophage infiltration through repression of FAK signaling.
총저자명 Jong Kyu WooYeong-Su JangJu-Hee KangJong-Ik HwangJe Kyung SeongSang-Jin LeeSejin JeonGoo Taeg OhHo-Young LeeSeung Hyun Oh
학술지명 Oncotarget 게재권(호) 7(20)
저널구분 - 페이지수 29592-29604
참여연구원 오승현 연구책임자 성제경
과제기여도 50 PMID 27127177
사사기관수 - IF (년도) 6.359
제1저자 우종규 교신저자 오승현
공동저자 -
초록
Macrophage infiltration promotes tumorigenesis. However, the macrophage infiltration regulatory molecules have not been fully determined. Nerve injury-induced protein 1 (ninjurin1) is a homophilic cell surface adhesion molecule that plays an important role in cell migration and attachment. Although ninjurin1 is believed to play a role in several malignancies, it is unclear whether ninjurin1 expression contributes to cancer progression. We used transgenic mice (tg mice) that overexpressed ninjurin1 on macrophages. We subjected ninjurin1 tg mice to a well-known mouse model of colitis-associated colon cancer in which animals are treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). After AOM and DSS treatment, ninjurin1 tg mice developed fewer and smaller tumors compared with wild-type (wt) mice. Ninjurin1 tg mice also showed reduced infiltration of macrophages and suppressed angiogenesis in the tumor mass. We therefore explored whether ninjurin1 decreases macrophage migration into the tumor sites. After adoptive transfer to tumor-bearing recipients, wild type and ninjurin1 tg mice's peritoneal macrophages were freshly isolated and labeled with carboxyfluorescein succinimidyl ester (CFSE). As expected, compared with that of wt type macrophages, tumor infiltration of ninjurin1-overexpressing macrophages was significantly decreased. We also found that ninjurin1 overexpression suppressed FAK activity. In addition, knockdown of ninjurin1 enhanced FAK activity and migration activity of RAW264.7 cells. Ninjurin1 overexpression on macrophage inhibits tumor growth by suppression of macrophage infiltration through repression of FAK signaling. Ninjurin1 is a key regulator molecule for macrophage migration and Tumor-associated macrophages (TAM) mediated tumorigenesis in vivo.
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