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Runx3 in Immunity, Inflammation and Cancer

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RUNX Proteins in Development and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 962))

Abstract

In this chapter we summarize the pros and cons of the notion that Runx3 is a major tumor suppressor gene (TSG). Inactivation of TSGs in normal cells provides a viability/growth advantage that contributes cell-autonomously to cancer. More than a decade ago it was suggested that RUNX3 is involved in gastric cancer development, a postulate extended later to other epithelial cancers portraying RUNX3 as a major TSG. However, evidence that Runx3 is not expressed in normal gastric and other epithelia has challenged the RUNX3-TSG paradigm. In contrast, RUNX3 is overexpressed in a significant fraction of tumor cells in various human epithelial cancers and its overexpression in pancreatic cancer cells promotes their migration, anchorage-independent growth and metastatic potential. Moreover, recent high-throughput quantitative genome-wide studies on thousands of human samples of various tumors and new investigations of the role of Runx3 in mouse cancer models have unequivocally demonstrated that RUNX3 is not a bona fide cell-autonomous TSG. Importantly, accumulating data demonstrated that RUNX3 functions in control of immunity and inflammation, thereby indirectly influencing epithelial tumor development.

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Acknowledgement

The work was supported by the Israel Science Foundation (ISF) individual grant to YG and DL. We thank Elsevier publishers for permission to adapt and re-use in this review data we have previously published included in doi:10.1016/j.bbcan.2015.01.004 (Lotem et al. 2015).

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Authors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel

    Joseph Lotem, Ditsa Levanon, Varda Negreanu, Omri Bauer, Shay Hantisteanu, Joseph Dicken & Yoram Groner

  2. Compugen Ltd, Holon, Israel

    Joseph Dicken

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  1. Joseph Lotem
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  2. Ditsa Levanon
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  3. Varda Negreanu
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  4. Omri Bauer
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  5. Shay Hantisteanu
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  6. Joseph Dicken
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  7. Yoram Groner
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Correspondence to Yoram Groner .

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Editors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

    Yoram Groner

  2. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Yoshiaki Ito

  3. Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA

    Paul Liu

  4. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom

    James C. Neil

  5. Department of Cell and Development Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Nancy A. Speck

  6. Mayo Clinic, Rochester, Minnesota, USA

    Andre van Wijnen

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Lotem, J. et al. (2017). Runx3 in Immunity, Inflammation and Cancer. In: Groner, Y., Ito, Y., Liu, P., Neil, J., Speck, N., van Wijnen, A. (eds) RUNX Proteins in Development and Cancer. Advances in Experimental Medicine and Biology, vol 962. Springer, Singapore. https://doi.org/10.1007/978-981-10-3233-2_23

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