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Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development

Oncogene volume 32, pages 2499–2509 (2013)Cite this article

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Abstract

Clinical studies have defined the core ‘genetic blueprint’ of a cancer cell, but this information does not necessarily predict the cancer phenotype. Signalling hubs that mediate such phenotype have been identified largely using OMICS platforms that measure dynamic molecular changes within the cancer cell landscape. The pro-oncogenic protein anterior gradient 2 (AGR2) is a case in point; AGR2 has been shown using a range of expression platforms to be involved in asthma, inflammatory bowel disease, cell transformation, cancer drug resistance and metastatic growth. AGR2 protein is also highly overexpressed in a diverse range of human cancers and can be secreted and detected in extracellular fluids, thus representing a compelling pro-oncogenic signalling intermediate in human cancer. AGR2 belongs to the protein disulphide isomerase family with all the key features of an endoplasmic reticulum-resident protein—this gives clues into how it might function as an oncoprotein through the regulation of protein folding, maturation and secretion that can drive metastatic cell growth. In this review, we will describe the known aspects of AGR2 molecular biology, including gene structure and regulation, emerging protein interaction networks and how its subcellular localization mediates its biological functions. We will finally review the cases of AGR2 expression in human cancers, the pathophysiological consequences of AGR2 overexpression, its potential role as a tumour biomarker that predicts the response to therapy and how the AGR2 pathway might form the basis for drug discovery programmes aimed at targeting protein folding/maturation pathways that mediate secretion and metastasis.

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Acknowledgements

We apologize to authors whose work has not been cited here owing to space limitations. This work was supported by grants from INSERM, INCa, Ligue contre le Cancer, Association pour la Recherche sur le Cancer (EC), Ligue contre le Cancer and a Chaire mixte Inserm—Univ. Bordeaux (FD), GACR number P301/10/1615 (RH), IGA MZ CR number NT/13794-4/2012 (BV) and by the European Regional Development Fund (RECAMO CZ.1.05/2.1.00/03.0101) (BV, RH, EM), and Cancer Research UK, MRC and BBSRC (TH).

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Authors and Affiliations

  1. INSERM U1053, Bordeaux, France

    E Chevet & A Mulot

  2. Université Bordeaux-Segalen, Bordeaux, France

    E Chevet & A Mulot

  3. Centre de recherche Cardio-Thoracique de Bordeaux, Université Bordeaux-Segalen, Bordeaux, France

    D Fessart & F Delom

  4. INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France

    D Fessart & F Delom

  5. Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic

    B Vojtesek, R Hrstka & E Murray

  6. p53 Signal Transduction Laboratories, Cell Signalling Unit, Institute of Genetics and Molecular Medicine, Cancer Research Centre, University of Edinburgh, Edinburgh, UK

    E Murray, T Gray & T Hupp

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  1. E Chevet
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Chevet, E., Fessart, D., Delom, F. et al. Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development. Oncogene 32, 2499–2509 (2013). https://doi.org/10.1038/onc.2012.346

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