MTA2 promotes the metastasis of esophageal squamous cell carcinoma via EIF4E-Twist feedback loop.
MTA2 promotes the metastasis of esophageal squamous cell carcinoma via EIF4E-Twist feedback loop.
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MTA2通过EIF4E-Twist反馈环促进食管鳞状细胞癌的转移
DOI：
10.1111/cas.14778
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发表时间：
2021-03
期刊：
影响因子：
5.7
通讯作者：
Shan BE
中科院分区：
文献类型：
--
作者：
Dai SL;Wei SS;Zhang C;Li XY;Liu YP;Ma M;Lv HL;Zhang Z;Zhao LM;Shan BE
转移相关蛋白2（MTA 2）在许多类型的癌症中经常扩增;然而，MTA 2在食管鳞状细胞癌（ESCC）中的作用和潜在的分子机制仍然未知。在此，我们报道了MTA 2在食管鳞癌组织和细胞中的高表达，并与食管鳞癌患者的恶性特征和不良预后密切相关。通过体外和体内实验，我们证明了MTA 2显著促进ESCC生长，转移和上皮-间质转化（EMT）进展。结合基因表达谱芯片的整合分析表明，MTA 2可以与真核起始因子4 E（EIF 4 E）相互作用，而EIF 4 E正调控EMT的主要调控因子Twist的表达。此外，染色质免疫沉淀的结果显示，MTA 2被Twist募集到E‐cadherin启动子上，从而降低了启动子区域的乙酰化水平，从而抑制了E‐cadherin的表达，随后促进了ESCC的侵袭性进展。总的来说，我们的研究提供了新的证据，证明MTA 2通过新的EIF 4 E-Twist正反馈回路在ESCC转移中发挥积极作用，这可能为ESCC的管理提供潜在的治疗靶点。我们发现食管鳞癌中MTA 2的表达上调与患者的恶性特征和较差的生存率显著相关。MTA 2在ESCC中的异常表达通过一种新的EIF 4 E-Twist正反馈环促进ESCC细胞的增殖、转移和EMT表型。
Metastasis‐associated protein 2 (MTA2) is frequently amplified in many types of cancers; however, the role and underlying molecular mechanism of MTA2 in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we reported that MTA2 is highly expressed in ESCC tissue and cells, and is closely related to the malignant characteristics and poor prognosis of patients with ESCC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promoted ESCC growth, metastasis, and epithelial‐mesenchymal transition (EMT) progression. This integrative analysis combined with expression microarray showed that MTA2 could interact with eukaryotic initiation factor 4E (EIF4E), which positively regulates the expression of Twist, known as a master regulator of EMT. Moreover, the results of chromatin immunoprecipitation revealed that MTA2 was recruited to the E‐cadherin promoter by Twist, which reduced the acetylation level of the promoter region and thus inhibited expression of E‐cadherin, and subsequently promoted the aggressive progression of ESCC. Collectively, our study provided novel evidence that MTA2 plays an aggressive role in ESCC metastasis by a novel EIF4E‐Twist positive feedback loop, which may provide a potential therapeutic target for the management of ESCC. We demonstrated that the upregulation of MTA2 in ESCC was significantly correlated with malignant characteristics and poor survival probability of patients. The abnormal expression of MTA2 in ESCC contributed to the proliferation, metastasis, and EMT phenotype of ESCC cells through a novel EIF4E‐Twist positive feedback loop.
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影响因子：
3.8
作者：
Covington, Kyle R.;Brusco, Lauren;Barone, Ines;Tsimelzon, Anna;Selever, Jennifer;Corona-Rodriguez, Arnoldo;Brown, Powel;Kumar, Rakesh;Hilsenbeck, Susan G.;Fuqua, Suzanne A. W.
通讯作者：
Fuqua, Suzanne A. W.
影响因子：
8
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通讯作者：
Sonenberg N
影响因子：
5
作者：
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通讯作者：
Gottfried, Maya
影响因子：
9.2
作者：
Covington, Kyle R.;Fuqua, Suzanne A. W.
通讯作者：
Fuqua, Suzanne A. W.
影响因子：
--
作者：
Chen, Da-Wei;Fan, Yao-Fu;Jiang, Xiao-Xiao
通讯作者：
Jiang, Xiao-Xiao