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.
基金:
Ministry of Sciences & Technology of China [2013CB 910900]; National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81372309, 81402376, 31671415, 31601114, 81402177]; Shanghai Committee of Science and TechnologyShanghai Science & Technology Committee [13JC1401302, 15410724200]; Shanghai Municipal Commission of Health and Family Planning [201440426]; Science and Technology Commission of Changning District of Shanghai [CNKW2014F01]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2015M570369]
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.
推荐引用方式(GB/T 7714):
Jia H.,Song L.,Cong Q.,et al.The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network[J].ONCOGENE.2017,36(19):2655-2666.doi:10.1038/onc.2016.418.
APA:
Jia, H.,Song, L.,Cong, Q.,Wang, J.,Xu, H....&Hou, Z..(2017).The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network.ONCOGENE,36,(19)
MLA:
Jia, H.,et al."The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network".ONCOGENE 36..19(2017):2655-2666