ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR/AKT/GSK3β/β-Catenin Signaling Pathway.
ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR/AKT/GSK3β/β-Catenin Signaling Pathway.
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ATF3通过停用EGFR/AKT/GSK3β/β-catenin信号通路来抑制透明细胞肾细胞癌的生长和转移。
DOI：
10.3389/fcell.2021.618987
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发表时间：
2021
影响因子：
5.5
通讯作者：
Qin X
中科院分区：
文献类型：
--
作者：
Gao S;Gao L;Wang S;Shi X;Yue C;Wei S;Zuo L;Zhang L;Qin X
透明细胞肾细胞癌（Clear cell renal cell carcinoma，ccRCC）是东亚地区最常见的恶性肿瘤之一，发病率和死亡率高。越来越多的证据表明，ATF 3与肿瘤进展相关。采用qPCR方法检测93例ccRCC患者组织中ATF 3的表达，其中包括24例配对的正常组织和肿瘤组织，并通过Western blotting和免疫组化方法进一步比较ATF 3的表达。慢病毒用于过表达或敲减ATF 3，并且通过CCK 8测定、集落形成测定、伤口愈合测定、侵袭测定和流式细胞术分析随后的功能改变。通过基因集富集分析（GSEA）分析ATF 3影响的潜在机制，并使用蛋白质印迹、侵袭试验或免疫荧光染色进行验证。此外，使用异种移植小鼠模型来评估ATF 3的体内功能。与邻近正常组织相比，ccRCC中ATF 3的表达显着降低。通过在体外测定中进行的功能获得和丧失实验，我们发现ATF 3可以调节ccRCC细胞增殖、周期进展、迁移和侵袭。在体内研究中，异种移植物小鼠模型揭示了ATF 3过表达可以抑制ccRCC的生长。抑制ATF 3表达可增加β-catenin的表达，促进β-catenin向细胞核的转移，其机制可能与EGFR/AKT/GSK 3 β信号通路有关。ATF 3可作为一种独立的保护因子抑制ccRCC的进展。ccRCC的潜在治疗策略包括靶向ATF 3/EGFR/AKT/GSK 3 β/β−catenin信号通路。
Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant cancers in East Asia, with high incidence and mortality. Accumulating evidence has shown that ATF3 is associated with tumor progression. Using qPCR, the expression of ATF3 was detected in 93 patients with ccRCC, including 24 paired normal and tumor tissues, which were used to further compare ATF3 expression through western blotting and immunohistochemistry. Lentivirus was used for the overexpression or knockdown of ATF3, and the consequent alteration in function was analyzed through CCK8 assay, colony formation assay, wound healing assay, invasion assay, and flow cytometry. The potential mechanism affected by ATF3 was analyzed through gene set enrichment analysis (GSEA) and verified using western blotting, invasion assay, or immunofluorescence staining. Furthermore, a xenograft mouse model was used to assess the function of ATF3 in vivo. ATF3 expression was significantly decreased in ccRCC compared to that in adjacent normal tissues. Through gain- and loss-of-function experiments performed in an in vitro assay, we found that ATF3 could regulate ccRCC cell proliferation, cycle progression, migration, and invasion. In the in vivo study, the xenograft mouse model revealed that ATF3 overexpression can inhibit the growth of ccRCC. Moreover, the mechanism analysis showed that suppression of ATF3 could lead to an increase the expression of β-catenin and promote β-catenin transfer to the nucleus, and might be affected by EGFR/AKT/GSK3β signaling. ATF3 could be utilized as an independent protective factor to inhibit the progression of ccRCC. Potential treatment strategies for ccRCC include targeting the ATF3/EGFR/AKT/GSK3β/β−catenin signaling pathway.
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DOI：
10.1136/bmj.g4797
发表时间：
2014-11-10
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Jonasch E;Gao J;Rathmell WK
通讯作者：
Rathmell WK
影响因子：
64.5
作者：
Rosenbluh J;Nijhawan D;Cox AG;Li X;Neal JT;Schafer EJ;Zack TI;Wang X;Tsherniak A;Schinzel AC;Shao DD;Schumacher SE;Weir BA;Vazquez F;Cowley GS;Root DE;Mesirov JP;Beroukhim R;Kuo CJ;Goessling W;Hahn WC
通讯作者：
Hahn WC
影响因子：
2.9
作者：
Li J;Yang Z;Chen Z;Bao Y;Zhang H;Fang X;Yang W
通讯作者：
Yang W
影响因子：
2
作者：
Hashmi AA;Hussain ZF;Irfan M;Khan EY;Faridi N;Naqvi H;Khan A;Edhi MM
通讯作者：
Edhi MM
影响因子：
50.3
作者：
Gargiulo, Gaetano;Cesaroni, Matteo;van Lohuizen, Maarten
通讯作者：
van Lohuizen, Maarten