Differentiated embryonic chondrocyte expressed gene-1 (DEC1) enhances the development of colorectal cancer with an involvement of the STAT3 signaling.
Differentiated embryonic chondrocyte expressed gene-1 (DEC1) enhances the development of colorectal cancer with an involvement of the STAT3 signaling.
复制标题
分化胚胎软骨细胞表达基因 1 (DEC1) 通过 STAT3 信号传导增强结直肠癌的发展。
DOI：
10.1016/j.neo.2022.100783
复制
发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Shan E;Huo Y;Wang H;Zhang Z;Hu J;Wang G;Liu W;Yan B;Hiroaki H;Yang J
结直肠癌（Colorectal cancer，CRC）是世界上第二大致死性恶性肿瘤，也是第三大常见恶性肿瘤.据预测，到2040年，CRC的年度新发病例将增加63%，这将在未来几十年构成更大的健康挑战。这项研究将DEC 1（分化的胚胎软骨细胞表达基因1）与CRC的发病机制联系起来。基于对患者样本和数据库数据的分析，DEC 1在CRC中的表达远高于邻近正常组织。DEC 1高表达的CRC患者生存期较短。氧化偶氮甲烷/硫酸葡聚糖的致癌方案在DEC 1 +/+小鼠中诱导的肿瘤数量比DEC 1 −/−小鼠更多，且肿瘤尺寸更大。DEC 1的过表达增加了增殖和抗凋亡相关基因的表达，但降低了促凋亡基因的水平。从机制上讲，这项研究表明，DEC 1在功能上与IL-6/STAT 3信号通路（白细胞介素-6/信号转导和转录激活因子3）成环。IL-6诱导DEC 1，DEC 1增强STAT 3的磷酸化，导致pSTAT 3/STAT 3比率增加。DEC 1和STAT 3存在于相互的免疫复合物中，指向物理相互作用（推测与pSTAT 3）。这些发现证实DEC 1是CRC增强子。这种增强主要通过IL-6/STAT 3途径实现。DEC 1和STAT 3之间的物理相互作用可能会成为制定CRC预防和治疗干预策略的基础。
Colorectal cancer (CRC) is the second deadly and the third most common malignancy worldwide. It has been projected that annual new cases of CRC will increase by 63% in 2040, constituting an even greater health challenge for decades to come. This study has linked DEC1 (differentiated embryonic chondrocyte expressed gene 1) to the pathogenesis of CRC. Based on the analysis of patient samples and database data, DEC1 is expressed much higher in CRC than the adjacent normal tissues. CRC patients with higher DEC1 expression have a shorter survival time. The carcinogenesis protocol with azoxymethane/dextran sulfate induces a higher number of tumors with larger sizes in DEC1+/+ than DEC1−/− mice. Overexpression of DEC1 increases the expression of proliferation- and antiapoptosis-related genes, but decreases the level of proapoptotic genes. Mechanistically, this study has shown that DEC1 is functionally looped to the IL-6/STAT3 signaling pathway (interleukin-6/signal transducer and activator of transcription 3). IL-6 induces DEC1, and DEC1 enhances the phosphorylation of STAT3, resulting in increased pSTAT3/STAT3 ratio. DEC1 and STAT3 are present in reciprocal immunocomplexes, pointing to physical interactions (presumably with pSTAT3). These findings establish that DEC1 is a CRC enhancer. The enhancement is achieved largely through the IL-6/STAT3 pathway. The potential of the physical interaction between DEC1 and STAT3 will likely serve as a foundation to develop intervention strategies for CRC prevention and therapy.
登录
查看更多内容
影响因子：
8.8
作者：
Nagasaki, T.;Hara, M.;Nakanishi, H.;Takahashi, H.;Sato, M.;Takeyama, H.
通讯作者：
Takeyama, H.
影响因子：
4.4
作者：
Miyazaki, Kazuko;Miyazaki, Masaki;Honda, Hiroaki
通讯作者：
Honda, Hiroaki
影响因子：
8
作者：
Ivanov, S. V.;Salnikow, K.;Lerman, M. I.
通讯作者：
Lerman, M. I.
影响因子：
4
作者：
Lin Y;He Z;Ye J;Liu Z;She X;Gao X;Liang R
通讯作者：
Liang R
影响因子：
4.1
作者：
Li, YX;Song, XL;Yan, BF
通讯作者：
Yan, BF