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The Functional Interplay Between Pro-oncogenic RUNX2 and Hypoxia-Inducible Factor-1α (HIF-1α) During Hypoxia-Mediated Tumor Progression

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Regulation of Signal Transduction in Human Cell Research

Part of the book series: Current Human Cell Research and Applications ((CHCRA))

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Abstract

Solid tumor tissues often have functional and phenotypical heterogeneities, arising at least in part from the local hypoxic tumor microenvironment (generally O2 concentration is less than 2%). The elevated level of hypoxia is tightly associated with genetic instability, tumor progression, drug resistance, and/or poor clinical outcome after treatment, indicating that hypoxia exerts a strong selection pressure for the survival of cancer stem cells (CSCs) within tumors and also permits their maintenance. Thus, it has become urgent to precisely clarify the molecular basis of how hypoxia could contribute to the acquisition and/or maintenance of the aggressive phenotypes of this deadly disease. Meanwhile, cells keep genomic integrity to avoid genetic instability-mediated tumorigenesis through the proper stress response under normoxia. Upon hypoxia, hypoxia-inducible factor-1α (HIF-1α) which has an O2-sensing ability accumulates and then facilitates tumor development through an induction of vascular endothelial growth factor (VEGF)-dependent angiogenesis. Therefore, the hypoxic HIF-1α/VEGF regulatory axis plays a vital role during the malignant tumor progression. Intriguingly, pro-oncogenic runt-related transcription factor 2 (RUNX2) has an ability to stimulate HIF-1α-mediated induction of VEGF. Recently, we have found for the first time that RUNX2 contributes to the acquisition of drug-resistant phenotype of malignant tumor cells. In this review, we focus on the functional interplay between HIF-1α/VEGF and RUNX2 within the hypoxic tumor microenvironment. Finally, we would like to discuss the potential therapeutic strategy targeting this tumor hypoxia.

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Acknowledgments

The authors are grateful to Dr. Hiroki Nagase for his helpful discussions.

Conflicts of Interest

The authors have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba, Japan

    Toshinori Ozaki, Mizuyo Nakamura, Takehiko Ogata, Meijie Sang & Osamu Shimozato

  2. Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan

    Meijie Sang

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  1. Toshinori Ozaki
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  2. Mizuyo Nakamura
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  3. Takehiko Ogata
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  4. Meijie Sang
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  5. Osamu Shimozato
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Correspondence to Toshinori Ozaki .

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Editors and Affiliations

  1. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan

    Nariyoshi Shinomiya

  2. Department of Pathology, University of Miyazaki, Miyazaki, Miyazaki, Japan

    Hiroaki Kataoka

  3. Department of Biomedical Sciences, Center of Excellence for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson, Tennessee, USA

    Qian Xie

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Ozaki, T., Nakamura, M., Ogata, T., Sang, M., Shimozato, O. (2018). The Functional Interplay Between Pro-oncogenic RUNX2 and Hypoxia-Inducible Factor-1α (HIF-1α) During Hypoxia-Mediated Tumor Progression. In: Shinomiya, N., Kataoka, H., Xie, Q. (eds) Regulation of Signal Transduction in Human Cell Research. Current Human Cell Research and Applications. Springer, Singapore. https://doi.org/10.1007/978-981-10-7296-3_5

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  • DOI: https://doi.org/10.1007/978-981-10-7296-3_5

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