TR4 nuclear receptor enhances prostate cancer initiation via altering the stem cell population and EMT signals in the PPARG-deleted prostate cells.
TR4 nuclear receptor enhances prostate cancer initiation via altering the stem cell population and EMT signals in the PPARG-deleted prostate cells.
复制标题
DOI：
10.18632/oncoscience.121
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Chang C
中科院分区：
文献类型：
--
作者：
Lin SJ;Yang DR;Wang N;Jiang M;Miyamoto H;Li G;Chang C
最近的一项研究表明，TR4核受体可能通过调节DNA损伤/修复系统来抑制前列腺癌（PCa）的发生。敲除过氧化物酶体增殖体激活受体（PPARG），一种与TR4具有相似配体/激活剂的核受体，促进PCa的起始。我们发现9%的PCa患者有一个PPARG缺失等位基因。来自体外细胞系和体内小鼠模型的结果表明，当PPARG被删除或被拮抗剂GW9662抑制时，在前列腺细胞中，TR4的作用可能从抑制因子转变为增强因子。机制解剖发现，在缺乏PPARG的情况下靶向TR4可能会改变干细胞群和上皮-间质转化（EMT）信号。总之，这些结果表明，TR4是否可以增强或抑制PCa的启动可能取决于PPARG的可用性以及未来通过靶向PPARG来对抗PPARG相关疾病的潜在治疗方法，可能需要考虑在PCa启动过程中TR4转换角色的潜在副作用。
A recent report indicated that the TR4 nuclear receptor might suppress the prostate cancer (PCa) initiation via modulating the DNA damage/repair system. Knocking-out peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that shares similar ligands/activators with TR4, promoted PCa initiation. Here we found 9% of PCa patients have one allele of PPARG deletion. Results from in vitro cell lines and in vivo mouse model indicated that during PCa initiation TR4 roles might switch from suppressor to enhancer in prostate cells when PPARG was deleted or suppressed (by antagonist GW9662). Mechanism dissection found targeting TR4 in the absence of PPARG might alter the stem cell population and epithelial-mesenchymal transition (EMT) signals. Together, these results suggest that whether TR4 can enhance or suppress PCa initiation may depend on the availability of PPARG and future potential therapy via targeting PPARG to battle PPARG-related diseases may need to consider the potential side effects of TR4 switched roles during the PCa initiation.