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Role of Hypoxia-Inducible Factor (HIF) in Liver Cancer

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Book cover Role of Transcription Factors in Gastrointestinal Malignancies

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Abstract

Liver cancer is one of the major causes of cancer-related deaths in the United States, accounting for 4.5% of the total estimated cancer deaths in 2016 and standing as the second leading cause of cancer-related deaths in men worldwide in 2012. There are two major types of primary liver cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). The most common type of primary liver cancer is HCC, which begins in hepatocytes and accounts for approximately 75% of all liver cancers. Hypoxia, a condition of oxygen deprivation in the tissue, is a common feature of the cancer microenvironment due to increased cell proliferation and limited blood supply. Hypoxia-inducible factor-1 (HIF-1) was the first transcription factor discovered to regulate a wide range of target genes involved in many cellular processes in response to low oxygen levels. HIF-1 is a heterodimeric protein complex composed of two different subunits, α and β. During a condition of hypoxia, HIF-1 heterodimer activates target genes that contain a hypoxia response element (HRE) in the promoter region. The overexpression of HIF-1 is frequently observed in many human solid tumors, including liver cancer, and is associated with tumor development, poor prognosis, and resistance to chemotherapy, suggesting that HIF-1 is a new therapeutic target in liver cancer treatment. In this chapter, we define the molecular mechanism that controls HIF-1 and how it maintains a variation of biological processes in hypoxic environments.

The original version of this chapter was revised. The book was inadvertently published without Abstracts and Keywords, which are now included in all the chapters. An erratum to this chapter can be found at https://doi.org/10.1007/978-981-10-6728-0_39

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering, College of Life and Health Sciences, Hoseo University, Asan, Chungnam, Republic of Korea

    Inho Choi

  2. Rice University, Houston, TX, USA

    Saipriya Lammata

  3. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA-30322, USA

    Neha Merchant

  4. Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Dongkyoo Park

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  1. Inho Choi
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  2. Saipriya Lammata
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  3. Neha Merchant
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  4. Dongkyoo Park
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Correspondence to Dongkyoo Park .

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Editors and Affiliations

  1. Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia, USA

    Ganji Purnachandra Nagaraju

  2. Department of Biotechnology, Krishna University, Machilipatnam, Andhra Pradesh, India

    Pallaval Veera Bramhachari

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Choi, I., Lammata, S., Merchant, N., Park, D. (2017). Role of Hypoxia-Inducible Factor (HIF) in Liver Cancer. In: Nagaraju, G., Bramhachari, P. (eds) Role of Transcription Factors in Gastrointestinal Malignancies. Springer, Singapore. https://doi.org/10.1007/978-981-10-6728-0_35

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