E2A suppresses invasion and migration by targeting YAP in colorectal cancer cells.
E2A suppresses invasion and migration by targeting YAP in colorectal cancer cells.
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E2A 通过靶向结直肠癌细胞中的 YAP 来抑制侵袭和迁移。
DOI：
10.1186/1479-5876-11-317
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发表时间：
2013-12-26
影响因子：
7.4
通讯作者：
Zheng M
中科院分区：
文献类型：
--
作者：
Zhao H;Huang A;Li P;Quan Y;Feng B;Chen X;Mao Z;Zhu Z;Zheng M
E2a基因编码两个碱性螺旋-环-螺旋(BHLH)转录因子E12和E47，是B淋巴系造血的调节因子和淋巴瘤的抑制因子。研究发现，E47蛋白可降低E-钙粘蛋白的表达，并诱导上皮-间充质转化(EMT)。然而，E2A在结直肠癌转移中的作用仍不清楚。采用定量逆转录聚合酶链式反应(qRT-PCR)和半定量逆转录聚合酶链式反应(Semi-qRT-PCR)检测大肠癌组织和结直肠癌细胞中E2AmRNA的表达。用RNAi技术下调E2a的表达，免疫印迹法检测蛋白水平的变化。用Transwell法检测细胞侵袭和迁移能力，分别用加或不加基膜基质的细胞培养片。转移性结直肠癌组织中E2a的表达降低。侵袭和迁移实验显示，下调E2A可增加大肠癌细胞的转移能力，而强制表达E12或E47则可抵消这一影响。E12和E47均可抑制E2A下调所致的EMT。此外，YAP是E2A的下游靶标，抑制YAP可抑制E2A缺乏的亲迁移/侵袭。我们的结果表明，E2A通过抑制YAP的表达抑制了CRC细胞的转移，至少是部分地，如果不是全部的话。
E2A gene, which encodes two basic helix–loop–helix (bHLH) transcription factors E12 and E47, has been identified as regulator of B lymphoid hematopoiesis and suppressor of lymphoma. E47 protein was found to decrease E-cadherin expression and induce epithelial-mesenchymal transition (EMT). However, the role of E2A in colorectal cancer (CRC) metastasis is still elusive. qRT-PCR and semi-qRT-PCR were performed to determine mRNA level of E2A in CRC specimens and colorectal cancer cells. RNAi was employed to downregulate E2A expression and subsequent protein level change was evaluated by immunoblot. Cell invasion and migration capacity were detected by transwell assay using cell culture inserts with or without basement membrane matrix, respectively. E2A expression was decreased in metastatic CRC tissues. Invasion and migration assays showed downregulation of E2A increased metastatic capacity of CRC cells while forced expression of E12 or E47 could offset this effect. Both E12 and E47 suppressed EMT induced by E2A downregulation. Moreover, Yes-Associated Protein (YAP) was a downstream target of E2A and suppression of YAP inhibited the pro-migration/invasion of E2A deficiency. Our results suggest that E2A suppresses CRC cell metastasis, at least partially if not all, by inhibiting YAP expression.
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影响因子：
4.8
作者：
Konsavage, Wesley M., Jr.;Kyler, Sydney L.;Yochum, Gregory S.
通讯作者：
Yochum, Gregory S.
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
7.3
作者：
Oh, Seo Jin;Shin, Jung-Ho;Kim, Tae Hoon;Lee, Hee Sun;Yoo, Jung-Yoon;Ahn, Ji Yeon;Broaddus, Russell R.;Taketo, Makoto M.;Lydon, John P.;Leach, Richard E.;Lessey, Bruce A.;Fazleabas, Asgerally T.;Lim, Jeong Mook;Jeong, Jae-Wook
通讯作者：
Jeong, Jae-Wook
DOI：
10.1073/pnas.96.3.996
发表时间：
1999-02-02
影响因子：
11.1
作者：
Engel, I;Murre, C
通讯作者：
Murre, C
影响因子：
64.5
作者：
BAIN, G;MAANDAG, ECR;MURRE, C
通讯作者：
MURRE, C