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Hypoxia Induced Stress Responses in Cancer and Cancer-Stem Cells

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Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

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Abstract

Oxygen is highly critical for the survival of complex organisms and lack of oxygen (hypoxia) promotes stress and death of the organism. However, cancer cells have evolved adaptive mechanisms to survive persistent pathological hypoxia experienced in the inner regions of the tumor. Normal cells rely on oxygen to meet the energy demands through mitochondrial oxidative phosphorylation, protein translation, and proper folding in the endoplasmic reticulum and for maintaining redox homeostasis. Therefore, cellular adaptive mechanisms will be employed by cancer cells through direct mechanisms such as down regulation of mitochondrial ATP production and autophagy to degrade the damage caused by hypoxia induced oxygen radicals. On the other hand, transcription factors such as hypoxia inducible factor-1 (HIF-1) and nuclear factor erythroid 2-related factor 2 (NRF2) enable the transcription of enzymes and stress responsive mechanisms to restore homeostasis indirectly. These stress response mechanisms promote resistance to cancer therapy. Hypoxia also influences other cells such as cancer stem cells (CSC) present in the hypoxic regions of the tumor. The current theory is CSCs are cells that initiate tumor with the ability to regenerate and hypoxia helps in their maintenance, thus contributes to drug resistance and relapse. Therefore, targeting hypoxia triggered adaptive mechanisms is intense area of research for drug development.

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Author information

Authors and Affiliations

  1. Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, India

    Sandhya Chipurupalli

  2. Diamantina Institute, The University of Queensland, Woolloongabba, Australia

    Snehlata Kumari

  3. Department of Experimental Medicine, University of Campania “L. Vanvitelli”, Naples, Italy

    Vincenzo Desiderio

  4. Cellular-Stress and Immune Response Laboratory, Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide, Australia

    Nirmal Robinson

Authors
  1. Sandhya Chipurupalli
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  2. Snehlata Kumari
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  3. Vincenzo Desiderio
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  4. Nirmal Robinson
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Corresponding author

Correspondence to Nirmal Robinson .

Editor information

Editors and Affiliations

  1. Department of Biochemistry and Biophysic, University of Kalyani Department of Biochemistry and Biophysic, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Dept of Veterinary Pathobiology, University of Missouri, College Vet, Columbia, MO, USA

    Bimal K Ray

  3. Saroj Gupta Cancer Centre & Research Ins, Kolkata, India

    Sushanta Roychowdhury

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Chipurupalli, S., Kumari, S., Desiderio, V., Robinson, N. (2021). Hypoxia Induced Stress Responses in Cancer and Cancer-Stem Cells. In: Chakraborti, S., Ray, B.K., Roychowdhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-4501-6_121-1

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  • DOI: https://doi.org/10.1007/978-981-15-4501-6_121-1

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  • Print ISBN: 978-981-15-4501-6

  • Online ISBN: 978-981-15-4501-6

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