Abelson interactor 1 splice isoform-L plays an anti-oncogenic role in colorectal carcinoma through interactions with WAVE2 and fulllength Abelson interactor 1  

作　　者：Kun Li Yi-Fan Peng Jing-Zhu Guo Mei Li Yu Zhang Jing-Yi Chen Ting-Ru Lin Xin Yu Wei-Dong Yu 

机构地区：[1]Department of Central Laboratory and Institute of Clinical Molecular Biology,Peking University People’s Hospital,Beijing 100044,China [2]Department of Gastroenterology,Peking University People’s Hospital,Peking University,Beijing 100044,China [3]Gastrointestinal Cancer Center,Unit III,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital and Institute,Beijing 100142,China [4]Department of Pediatrics,Peking University People’s Hospital,Beijing 100044,China [5]Department of Central Laboratory and Institute of Clinical Molecular Biology,Peking University People's Hospital,Beijing 100044,China [6]Department of Hepatobiliary Surgery,Peking University People’s Hospital,Beijing 100044,China

出　　处：《World Journal of Gastroenterology》2021年第15期1595-1615,共21页世界胃肠病学杂志（英文版）

基　　金：National Natural Science Foundation of China,No.30872923 and No.81672853;and Peking University People’s Hospital Scientific Research Development Found,No.RDH2020-11.

摘　　要：BACKGROUND Expression of the full-length isoform of Abelson interactor 1(ABI1),ABI1-p65,is increased in colorectal carcinoma(CRC)and is thought to be involved in one or more steps leading to tumor progression or metastasis.The ABI1 splice isoform-L(ABI1-SiL)has conserved WAVE2-binding and SH3 domains,lacks the homeodomain homologous region,and is missing the majority of PxxP-and Pro-rich domains found in full-length ABI1-p65.Thus,ABI1-SiL domain structure suggests that the protein may regulate CRC cell morphology,adhesion,migration,and metastasis via interactions with the WAVE2 complex pathway.AIM To investigate the potential role and underlying mechanisms associated with ABI1-SiL-mediated regulation of CRC.METHODS ABI1-SiL mRNA expression in CC tissue and cell lines was measured using both qualitative reverse transcriptase-polymerase chain reaction(RT-PCR)and realtime quantitative RT-PCR.A stably ABI1-SiL overexpressing SW480 cell model was constructed using Lipofectamine 2000,and cells selected with G418.Image J software,CCK8,and transwell assays were used to investigate SW480 cell surface area,proliferation,migration,and invasion.Immunoprecipitation,Western blot,and co-localization assays were performed to explore intermolecular interactions between ABI1-SiL,WAVE2,and ABI1-p65 proteins.RESULTS ABI1-SiL was expressed in normal colon tissue and was significantly decreased in CRC cell lines and tissues.Overexpression of ABI1-SiL in SW480 cells significantly increased the cell surface area and inhibited the adhesive and migration properties of the cells,but did not alter their invasive capacity.Similar to ABI1-p65,ABI1-SiL still binds WAVE2,and the ABI1-p65 isoform in SW480 cells.Furthermore,co-localization assays confirmed these intermolecular interactions.CONCLUSION These results support a model in which ABI1-SiL plays an anti-oncogenic role by competitively binding to WAVE2 and directly interacting with phosphorylated and non-phosphorylated ABI1-p65,functioning as a dominant-negative form of ABI1-p65.

关 键 词：Colon cancer Abelson interactor 1 isoform-L Cell adhesion Cell migration WAVE2 

分 类 号：R735.34[医药卫生—肿瘤]