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Runx3 and Cell Fate Decisions in Pancreas 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

The RUNX family transcription factors are critical regulators of development and frequently dysregulated in cancer. RUNX3, the least well characterized of the three family members, has been variously described as a tumor promoter or suppressor, sometimes with conflicting results and opinions in the same cancer and likely reflecting a complex role in oncogenesis. We recently identified RUNX3 expression as a crucial determinant of the predilection for pancreatic ductal adenocarcinoma (PDA) cells to proliferate locally or promulgate throughout the body. High RUNX3 expression induces the production and secretion of soluble factors that support metastatic niche construction and stimulates PDA cells to migrate and invade, while simultaneously suppressing proliferation through increased expression of cell cycle regulators such as CDKN1A/p21 WAF1/CIP1. RUNX3 expression and function are coordinated by numerous transcriptional and post-translational inputs, and interactions with diverse cofactors influence whether the resulting RUNX3 complexes enact tumor suppressive or tumor promoting programs. Understanding these exquisitely context-dependent tumor cell behaviors has the potential to inform clinical decision-making including the most appropriate timing and sequencing of local vs. systemic therapies.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M5-C800, Seattle, WA, 98109-1024, USA

    Martin C. Whittle & Sunil R. Hingorani M.D., Ph.D.

  2. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M5-C800, Seattle, WA, 98109-1024, USA

    Sunil R. Hingorani M.D., Ph.D.

  3. Division of Medical Oncology, University of Washington School of Medicine, Seattle, WA, 98195, USA

    Sunil R. Hingorani M.D., Ph.D.

Authors
  1. Martin C. Whittle
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  2. Sunil R. Hingorani M.D., Ph.D.
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Corresponding author

Correspondence to Sunil R. Hingorani M.D., Ph.D. .

Editor information

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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© 2017 Springer Nature Singapore Pte Ltd.

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Whittle, M.C., Hingorani, S.R. (2017). Runx3 and Cell Fate Decisions in Pancreas 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_21

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