SUMOylation of IQGAP1 promotes the development of colorectal cancer

SUMOylation of IQGAP1 promotes the development of colorectal cancer
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IQGAP1的SUMO化促进结直肠癌的发展

DOI:
10.1016/j.canlet.2017.09.046
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发表时间:
2017-12-28
期刊:
影响因子:
9.7
通讯作者:
Liang, Shufang
Liang, Shufang
中科院分区:
医学1区
文献类型:
--
作者:
Liang, Ziwei;Yang, Yanfang;Liang, Shufang

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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 IQGAPl SUMOylation is a novel regulatory mechanism to enhance tumorigenesis and development of CRC in vitro and in vivo. (c) 2017 Elsevier B.V. All rights reserved.