Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer.
Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer.
复制标题
DOI：
10.1038/s41467-018-04244-2
复制
发表时间：
2018-05-15
影响因子：
16.6
通讯作者：
Park YY
中科院分区：
文献类型：
--
作者：
Kang MH;Choi H;Oshima M;Cheong JH;Kim S;Lee JH;Park YS;Choi HS;Kweon MN;Pack CG;Lee JS;Mills GB;Myung SJ;Park YY
胃癌（GC）发展和预后的主要因素尚未很好地表征，导致缺乏有效的治疗靶点。为了确定潜在的分子靶点，我们分析了GC患者的基因表达数据，并确定了核受体ESRRG作为候选肿瘤抑制因子。ESRRG表达在胃癌中降低，是不良临床预后的预测因子。重要的是，ESRRG抑制GC细胞生长和肿瘤发生。基因表达谱表明，ESRRG通过抑制TCF4/LEF1与CCND1启动子的结合来拮抗Wnt信号。事实上，在GC患者中发现ESRRG水平与Wnt信号相关基因呈负相关。引人注目的是，ESRRG激动剂DY131抑制肿瘤生长并抑制Wnt信号基因的表达。因此，我们目前的研究结果表明，ESRRG在胃癌中作为Wnt信号通路的负调节因子发挥作用，是胃癌的潜在治疗靶点。我们对胃癌发生的分子机制知之甚少。本文作者发现，雌激素相关受体γ (ESRRG)在胃癌中是一种抑瘤因子，其抑瘤作用机制可能与抑制Wnt信号通路有关。
The principle factors underlying gastric cancer (GC) development and outcomes are not well characterized resulting in a paucity of validated therapeutic targets. To identify potential molecular targets, we analyze gene expression data from GC patients and identify the nuclear receptor ESRRG as a candidate tumor suppressor. ESRRG expression is decreased in GC and is a predictor of a poor clinical outcome. Importantly, ESRRG suppresses GC cell growth and tumorigenesis. Gene expression profiling suggests that ESRRG antagonizes Wnt signaling via the suppression of TCF4/LEF1 binding to the CCND1 promoter. Indeed, ESRRG levels are found to be inversely correlated with Wnt signaling-associated genes in GC patients. Strikingly, the ESRRG agonist DY131 suppresses cancer growth and represses the expression of Wnt signaling genes. Our present findings thus demonstrate that ESRRG functions as a negative regulator of the Wnt signaling pathway in GC and is a potential therapeutic target for this cancer. Very little is known regarding the molecular mechanisms involved in gastric cancer development. Here the authors show estrogen-related receptor gamma (ESRRG) is a tumor suppressor in gastric cancer and suggest the mechanism of this tumor suppression function involves the inhibition of Wnt signaling.
登录
查看更多内容
DOI：
10.1186/s13046-015-0150-9
发表时间：
2015-05-15
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Madhavan S;Gusev Y;Singh S;Riggins RB
通讯作者：
Riggins RB
影响因子：
4.7
作者：
Park, Yun-Yong;Jung, Sung Yun;Lee, Ju-Seog
通讯作者：
Lee, Ju-Seog
影响因子：
4.8
作者：
Kim, Hye-Jin;Kwon, Sojung;Lee, Jung Weon
通讯作者：
Lee, Jung Weon
影响因子：
--
作者：
Kumar, Premlata;Mendelson, Carole R.
通讯作者：
Mendelson, Carole R.
影响因子：
11.5
作者：
Ondrey, Frank
通讯作者：
Ondrey, Frank