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SUMOylation of IQGAP1 promotes the development of colorectal cancer.

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机构： [a]State Key Laboratory of Biotherapy and Cancer Center,West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, 3rd Section of People's South Road, Chengdu, 610041, PR China [b]Department of Urinary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China [c]Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, 100034, PR China [d]Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, 610041, PR China

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关键词： IQGAP1 Colorectal carcinoma SUMOylation SUMO1

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IQGAP1 is a conserved multifunctional protein implicated in tumorigenesis. An aberrant expression of IQGAP1 widely exists in many cancers, but the SUMOylation modification of IQGAP1 in carcinogenesis is unknown by now. Here we first time explore biological functions of IQGAP1 SUMOylation in promoting colorectal cancer progression in vitro and in vivo. The expression of IQGAP1 and its SUMOylation level are both increased in human colorectal carcinoma (CRC) cells and tissues. IQGAP1 is mainly SUMOylated by SUMO1 at the K1445 residue, which could stabilize IQGAP1 by reducing protein ubiquitination. IQGAP1 SUMOylation improves CRC cell growth, cell migration and tumorigenesis in vivo through activating the phosphorylation of ERK, MEK and AKT. While the SUMOylation site mutation at K1445 of IQGAP1 greatly reduces CRC cell proliferation, migration ability and tumor growth of CRC-xenograft mice by suppressing phosphorylation of ERK, MEK and AKT. Our findings discover the IQGAP1 SUMOylation is a novel regulatory mechanism to enhance tumorigenesis and development of CRC in vitro and in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

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出版当年[2017]版：

大类 | 2 区

医学

小类 | 2 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 2 区肿瘤学

第一作者：

第一作者机构： [a]State Key Laboratory of Biotherapy and Cancer Center,West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, 3rd Section of People's South Road, Chengdu, 610041, PR China

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通讯机构： [a]State Key Laboratory of Biotherapy and Cancer Center,West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, 3rd Section of People's South Road, Chengdu, 610041, PR China

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相关文献

[1]SUMOylation of IQGAP1 promotes the development of colorectal cancer. [2]MS-based strategies for identification of protein SUMOylation modification. [3][Clinicopathological features of early colorectal carcinoma]. [4]Protein SUMOylation modification and its associations with disease. [5]Small-Molecule Inhibitors Targeting Protein SUMOylation as Novel Anticancer Compounds. [6]Clinicopathological features of early colorectal carcinoma [7]SAE1 promotes human glioma progression through activating AKT SUMOylation-mediated signaling pathways [8]Role of CBX4 in the Colorectal Carcinoma Metastasis-Response [9]Protein SUMOylation modification and its associations with disease. [10]The Overexpression of IQGAP1 and β-Catenin Is Associated with Tumor Progression in Hepatocellular Carcinoma In Vitro and In Vivo.