SUMOylation of IQGAP1 promotes the development of colorectal cancer

• Published in: Cancer letters 2017-12, Vol.411, p.90-99
• Main Authors: Liang, Ziwei, Yang, Yanfang, He, Yu, Yang, Pengbo, Wang, Xixi, He, Gu, Zhang, Peng, Zhu, Hongxia, Xu, Ningzhi, Zhao, Xia, Liang, Shufang
• Format: Article
• Language: English
• Subjects: AKT protein; Animal tissues; Animals; Carcinogenesis; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - physiology; Cell proliferation; Cell Proliferation - physiology; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Deoxyribonucleic acid; DNA; HCT116 Cells; HEK293 Cells; Heterografts; Humans; Immunoglobulins; IQGAP1; IQGAP1 protein; Kinases; Male; Mice; Mice, Inbred BALB C; Phosphorylation; Plasmids; Proteins; Proteomics; ras GTPase-Activating Proteins - genetics; ras GTPase-Activating Proteins - metabolism; SUMO protein; SUMO1; SUMOylation; Transfection; Tumorigenesis; Ubiquitination; Xenografts
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.09.046

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. •IQGAP1 SUMOylation is increased in colorectal cancer (CRC) cells and tissues.•IQGAP1 is mainly SUMOylated by SUMO1 modification at the Lys1445 residue.•The SUMOylation stabilizes IQGAP1 by reducing its ubiquitination.•IQGAP1 SUMOylation increases tumorigenesis of CRC in vitro and in vivo by activating AKT-ERK signaling pathways.