β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition.
β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition.
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DOI：
10.3389/fcell.2021.650067
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发表时间：
2021
影响因子：
5.5
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Song Q;Han Z;Wu X;Wang Y;Zhou L;Yang L;Liu N;Sui H;Cai J;Ji Q;Li Q
肿瘤的复发和转移严重影响着患者的预后，而上皮间质转化（EMT）在促进肿瘤侵袭和转移中起着关键作用。已有研究表明β-arrestin 1在多种肿瘤中作为促癌因子发挥作用。然而，β-arrestin 1在结直肠癌（CRC）进展中的确切作用和机制仍有待阐明。本研究旨在探讨β-arrestin 1在结直肠癌转移中的作用机制。应用GSE 41258数据库对原发性和转移性结直肠癌组织中β-arrestin 1的表达进行研究，发现结直肠癌肝/肺转移患者中β-arrestin 1的表达水平较高，且β-arrestin 1的表达水平与结直肠癌患者的预后呈负相关。进一步的体外机制研究表明，β-arrestin 1通过激活Wingless/integration-1（Wnt）/β-catenin信号通路，调节EMT过程，从而促进结直肠癌细胞的迁移。用抑制剂ICG 001阻断Wnt/β-catenin信号通路可降低β-arrestin 1对结直肠癌EMT的促进作用。体内成像实验进一步证实了小鼠尾静脉注射β-arrestin 1对结直肠癌细胞肺转移的促进作用。本研究结果提示β-arrestin 1通过Wnt/β-catenin信号通路促进大肠癌转移中的EMT，为大肠癌转移提供了一个新的治疗靶点。
Recurrence and metastasis seriously affects the prognosis of patients with tumors, and the epithelial-to-mesenchymal transition (EMT) plays a key role in promoting tumor invasion and metastasis. Previous studies have showed that β-arrestin1 acted as a tumor-promoting factor in multiple types of tumor. However, the exact role and mechanism of β-arrestin1 in colorectal cancer (CRC) progression remains to be elucidated. Our research aimed to explore the potential mechanism underlying the role of β-arrestin1 in CRC metastasis. The expression of β-arrestin1 was investigated in both primary and metastatic CRC tissues using the GSE41258 database, and it was revealed that CRC patients with liver/lung metastasis had a higher expression level of β-arrestin1, and the expression level of β-arrestin1 was inversely correlated with the prognosis of CRC patients. Further in vitro mechanism studies indicated that β-arrestin1 had the ability to promote the migration of CRC cells through regulating the EMT process by activating Wingless/integration-1 (Wnt)/β-catenin signaling pathways. Blocking Wnt/β-catenin signaling with inhibitor ICG001 decreased the promoting effect of β-arrestin1 on EMT in CRC. In vivo imaging experiments further demonstrated the promoting effect of β-arrestin1 on the lung metastasis of CRC cells by tail vein injection in mice. The results of this paper suggest that β-arrestin1 promotes EMT via Wnt/β-catenin signaling pathway in CRC metastasis, and provides a novel therapeutic target for CRC metastasis.
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影响因子：
11.2
作者：
Pillai S;Trevino J;Rawal B;Singh S;Kovacs M;Li X;Schell M;Haura E;Bepler G;Chellappan S
通讯作者：
Chellappan S
影响因子：
4.8
作者：
Ge, L;Shenoy, SK;DeFea, K
通讯作者：
DeFea, K
DOI：
10.1073/pnas.0611356104
发表时间：
2007-04-17
影响因子：
11.1
作者：
Bryja, Vitezslav;Gradl, Dietmar;Schulte, Gunnar
通讯作者：
Schulte, Gunnar
Dickkopf-1抑制Wnt3a诱导的人晶状体上皮细胞迁移和上皮间质转化
影响因子：
3.4
作者：
Liu, Tingting;Zhang, Limin;Bao, Xiuli
通讯作者：
Bao, Xiuli
影响因子：
4.8
作者：
Mendez, Melissa G.;Kojima, Shin-Ichiro;Goldman, Robert D.
通讯作者：
Goldman, Robert D.