Tripartite motif-containing 9 promoted proliferation and migration of bladder cancer cells through CEACAM6-Smad2/3 axis.

IF 3.6 3区生物学 Q3 CELL BIOLOGY

Journal of Cell Communication and Signaling Pub Date : 2023-12-01 Epub Date: 2023-05-30 DOI:10.1007/s12079-023-00766-7

Zhao-Cun Zhang, Hai-Feng Zhao, Zhuang Sun, Yi Li, Ming-Lei Zhong, Bao-Hai Wang, Xian-Zhou Jiang

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引用次数: 1

Abstract

Studies have shown that tripartite motif-containing (TRIM) family proteins function as E3 ubiquitin ligases and play essential roles in cancer biology. In the present study, we validated a contribution of TRIM9 to bladder cancer progression. 296 patients derived from The Cancer Genome Atlas (TCGA) database and 22 clinical specimens were included, in which accumulated TRIM9 correlated with the poor prognosis and higher relapse in bladder patients. In vitro, TRIM9 promoted bladder cancer cells Biu-87 and T24 cell proliferation and migration. Meanwhile, overexpression of TRIM9 reduced the chemosensitivity in Biu-87 and T24 to mitomycin C (MMC) and gemcitabine (GEM). As an underlying mechanism, we found that TRIM9 stimulated carcinoembryonic antigen 6 (CEACAM6) upregulation, which further facilitated Smad2/3-matrix metalloproteinase 2 (MMP2) signaling activation both in vitro and in vivo. Those results indicated that TRIM9 facilitated bladder cancer development and chemoresistance by CEACAM6-Smad2/3 axis. TRIM9 and its associated molecules could be a potential diagnostic indicator and therapeutic target in bladder cancer.

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含三方基序的 9 通过 CEACAM6-Smad2/3 轴促进膀胱癌细胞的增殖和迁移。

研究表明，含三方基序（TRIM）家族蛋白具有 E3 泛素连接酶的功能，在癌症生物学中发挥着重要作用。在本研究中，我们验证了 TRIM9 对膀胱癌进展的贡献。研究纳入了来自癌症基因组图谱（TCGA）数据库的296名患者和22份临床标本，其中累积的TRIM9与膀胱癌患者的不良预后和高复发率相关。在体外，TRIM9能促进膀胱癌细胞Biu-87和T24的增殖和迁移。同时，TRIM9的过表达降低了Biu-87和T24对丝裂霉素C（MMC）和吉西他滨（GEM）的化疗敏感性。作为潜在机制，我们发现TRIM9刺激癌胚抗原6（CEACAM6）上调，这进一步促进了体外和体内Smad2/3-基质金属蛋白酶2（MMP2）信号的激活。这些结果表明，TRIM9通过CEACAM6-Smad2/3轴促进了膀胱癌的发展和化疗耐药性。TRIM9及其相关分子可能是膀胱癌的潜在诊断指标和治疗靶点。

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来源期刊

Journal of Cell Communication and Signaling CELL BIOLOGY-

CiteScore

6.40

自引率

4.90%

发文量

期刊介绍： The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.