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The Anti-Tumor Activity of E1A and its Implications in Cancer Therapy

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

The adenovirus type 5 E1A protein (E1A) plays a critical role in anti-cancer gene therapy and has been tested in clinical trials. The expression of E1A significantly reduces tumorigenesis, promotes cell death, and inhibits cancer cell mobility. Chemosensitization is one of the anti-tumor effects of E1A, increasing in vitro and in vivo sensitization of anti-cancer drugs, including cisplatin, gemcitabine, etoposide, doxorubicin, paclitaxel, and tumor necrosis factor-related apoptosis-inducing ligand and histone deacetylase inhibitors in different types of cancer cells. E1A also demonstrates anti-metastasis activity through various molecular mechanisms such as the repression of protease expression, suppression of HER2/neu and downregulation of microRNA (miR-520h). Moreover, E1A has been reported to reprogram transcription in tumor cells and stabilize tumor suppressors such as PP2A/C, p21 and p53. Because E1A plays a potentially significant role in anti-tumor therapy, there exists an urgent need to study the anti-cancer activities of E1A. This paper presents a review of our current understanding of the tumor-suppressive functions and molecular regulation of E1A, as well as the potential clinical applications of E1A.

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Acknowledgments

This work was supported by the National Science Council grant from Taiwan (NSC 102-2314-B-039-200, NSC 102-2314-B-038-028-MY3, NSC 101-2320-B-400-016-MY3); National Health Research Institutes grant from Taiwan (CA-102-PP-41); Ministry of Health and Welfare, Taiwan (DOH 102-TD-C-111-004).

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Authors and Affiliations

  1. Graduate Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, 11221, Taiwan

    Yi-Wen Chang

  2. Genomics Research Center, Academia Sinica, Taipei, Taiwan

    Yi-Wen Chang

  3. Graduate Institute of Cancer Biology, China Medical University, Taichung, 40402, Taiwan

    Mien-Chie Hung & Jen-Liang Su

  4. Department of Biotechnology, Asia University, Taichung, 41354, Taiwan

    Mien-Chie Hung & Jen-Liang Su

  5. Center for Molecular Medicine, China Medical University Hospital, Taichung, 40402, Taiwan

    Mien-Chie Hung & Jen-Liang Su

  6. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Mien-Chie Hung

  7. National Institute of Cancer Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan, Miaoli County, 35053, Taiwan

    Jen-Liang Su

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Chang, YW., Hung, MC. & Su, JL. The Anti-Tumor Activity of E1A and its Implications in Cancer Therapy. Arch. Immunol. Ther. Exp. 62, 195–204 (2014). https://doi.org/10.1007/s00005-014-0273-2

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