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

Oncogene volume 36, pages 2655–2666 (2017)Cite this article

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Abstract

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 IFNγ 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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Acknowledgements

We thank Dr Frank J Rauscher III for his critical reading and insightful suggestions, and Xinyu Hou for her technical support. This work was supported by the Ministry of Sciences & Technology of China (2013CB 910900); the National Science Foundation of China (grant Nos. 81372309, 81402376, 31671415, 31601114, 81402177); Shanghai Committee of Science and Technology (13JC1401302, 15410724200); Shanghai Municipal Commission of Health and Family Planning (No. 201440426); and Science and Technology Commission of Changning District of Shanghai No. CNKW2014F01); and the China Postdoctoral Science Foundation (No. 2015M570369).

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Author notes

  1. H Jia and L Song: These authors contributed equally to this work.

Authors and Affiliations

  1. Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China

    H Jia, L Song, J Wang, H Xu, Q Li, Y Zhang, X Zou, H Peng & Z Hou

  2. Digestive Endoscopy Center, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    H Jia, Y Chu, H Peng & Z Hou

  3. Department of Biochemistry & Molecular Cellular Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China

    H Jia, J Wang, H Xu, Q Li, Y Zhang, X Zou & Z Hou

  4. Department of General Surgery, The Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    L Song & B Wang

  5. Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institute, Ministry of Education, Shanghai Jiaotong University, Shanghai, China

    Q Cong

  6. Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    C Zhang & Y E Chin

  7. Institute of Cancer Stem cells, Dalian Medical University Cancer Center, Liaoning, China

    X Zhang & Z Li

  8. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China

    K Zhu

  9. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Z Hou

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  1. H Jia
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Correspondence to B Wang, H Peng or Z Hou.

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Jia, H., Song, L., Cong, Q. et al. The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network. Oncogene 36, 2655–2666 (2017). https://doi.org/10.1038/onc.2016.418

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  • DOI: https://doi.org/10.1038/onc.2016.418

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