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The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network

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机构: [1]Shanghai Jiao Tong Univ, Sch Med, Fac Basic Med, Hongqiao Inst Med,Shanghai Tongren Hosp, Shanghai, Peoples R China [2]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Digest Endoscopy Ctr, 1111 Xianxia Rd, Shanghai 200336, Peoples R China [3]Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cellular Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai, Peoples R China [4]Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Gen Surg, Shanghai 200011, Peoples R China [5]Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Shanghai, Peoples R China [6]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China [7]Dalian Med Univ, Canc Ctr, Inst Canc Stem Cells, Dalian, Liaoning, Peoples R China [8]Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai, Peoples R China [9]Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis Chinese Min, Shanghai, Peoples R China
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The LIM protein AJUBA is a scaffold protein participating in the regulation of cell adhesion, mitosis, DNA damage, cell differentiation, proliferation, migration and gene transcription. However, its roles in tumorigenesis and progression are poorly defined. Here, we report that AJUBA is highly expressed in colorectal cancer (CRC) and promotes CRC cell growth in culture and in xenografted mice via an inhibition of apoptosis. AJUBA represses the expression of IFIT2 gene, an interferon-stimulated gene and a known apoptosis inducer and tumour suppressor to mediate its resistance to apoptosis. Mechanistic investigations reveal that AJUBA specifically binds the FERM domain of JAK1 to dissociate JAK1 from the IFN gamma recepter, resulting in an inhibition of STAT1 phosporylation and concomitantly its nuclear translocation. Clinically, the level of AJUBA in CRC specimens is negatively correlated with the levels of IFIT2 and pSTAT1. Collectively, these studies demonstrate that AJUBA can promote CRC growth via inhibiting apoptosis and serve as a target for the therapeutics and a marker for diagnosis of CRC.

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出版当年[2016]版:
大类 | 1 区 医学
小类 | 1 区 遗传学 1 区 肿瘤学 2 区 生化与分子生物学 2 区 细胞生物学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 遗传学 2 区 细胞生物学 2 区 肿瘤学
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出版当年[2015]版:
Q1 ONCOLOGY Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 GENETICS & HEREDITY Q1 CELL BIOLOGY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CELL BIOLOGY Q1 GENETICS & HEREDITY Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2015版] 出版当年五年平均 出版前一年[2014版] 出版后一年[2016版]

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第一作者机构: [1]Shanghai Jiao Tong Univ, Sch Med, Fac Basic Med, Hongqiao Inst Med,Shanghai Tongren Hosp, Shanghai, Peoples R China [2]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Digest Endoscopy Ctr, 1111 Xianxia Rd, Shanghai 200336, Peoples R China [3]Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cellular Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai, Peoples R China
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通讯机构: [1]Shanghai Jiao Tong Univ, Sch Med, Fac Basic Med, Hongqiao Inst Med,Shanghai Tongren Hosp, Shanghai, Peoples R China [2]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Digest Endoscopy Ctr, 1111 Xianxia Rd, Shanghai 200336, Peoples R China [3]Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cellular Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai, Peoples R China [4]Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Gen Surg, Shanghai 200011, Peoples R China [9]Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis Chinese Min, Shanghai, Peoples R China [*1]Department of General Surgery, The Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China [*2]Digestive Endoscopy Center, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 Xianxia Rd, Shanghai 200336, China [*3]Department of Biochemistry and Molecular Cell Biology, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Rd, Building 7#, Room 110, Shanghai 200025, China.
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