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Hypoxia Inducible Factors in the Tumor Microenvironment As Therapeutic Targets of Cancer Stem Cells Publisher Pubmed



Hajizadeh F1, 2 ; Okoye I3 ; Esmaily M4 ; Ghasemi Chaleshtari M1 ; Masjedi A1 ; Azizi G5 ; Irandoust M1 ; Ghalamfarsa G6 ; Jadidiniaragh F7, 8
Authors
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Authors Affiliations
  1. 1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, T6G 2E1, Canada
  4. 4. Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  6. 6. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
  7. 7. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  8. 8. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Life Sciences Published:2019


Abstract

Cancer stem cells (CSC) constitute a small area of the tumor mass and are characterized by self-renewal, differentiation and the ability to promote the development of secondary chemo-resistant tumors. Self-renewal of CSCs is regulated through various signaling pathways including Hedgehog, Notch, and Wnt/β-catenin pathways. A few surface markers have been identified, which provide a means of targeting CSCs according to tumor type. Depending on the proximity of CSCs to the tumor hypoxic niche, hypoxia-inducible factors (HIFs) can play a critical role in modulating several CSC-related characteristics. For instance, the upregulation of HIF-1 and HIF-2 at tumor sites, which correlates with the expansion of CSCs and poor cancer prognosis, has been demonstrated. In this review, we will discuss the mechanisms by which hypoxia enhances the development of CSCs in the tumor microenvironment. Targeting HIFs in combination with other common therapeutics is pre-requisite for effective eradication of CSCs. © 2019
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