Stabilisation and Knockdown of HIF - Two Distinct Ways Comparably Important in Radiotherapy

Ströfer, Mareike; Jelkmann, Wolfgang; Metzen, Eric; Brockmeier, Ulf; Dunst, Jürgen; Depping, Reinhard

doi:10.1159/000335794

Cited by 16 publications

(19 citation statements)

References 31 publications

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“…High expression of HIF-1 enhances the resistance to radiation as assessed by clonogenic survival assay under normoxic and hypoxic conditions [53], whereas inactivation of HIF-1 signaling pathway by HIF-1α inhibitors or siRNA has been shown to increase the sensitivity of tumor to radiation therapy in vitro and in vivo [13,53,54]. Other experimental studies also revealed that HIF-1α deficiency in various cancer cells, including CSCs, are more susceptible to chemotherapeutics and ionizing radiation therapy than its wild type cells [15,45,55].…”

Section: Hypoxia Hif and Treatment Resistance In Tumormentioning

confidence: 99%

The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness

Bao

Azmi

Ali

et al. 2012

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

128

139

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Hypoxia is one of the fundamental biological phenomena that are intricately associated with the development and aggressiveness of a variety of solid tumors. Hypoxia-inducible factors (HIF) function as a master transcription factor, which regulates hypoxia responsive genes and has been recognized to play critical roles in tumor invasion, metastasis, and chemo-radiation resistance, and contributes to increased cell proliferation, survival, angiogenesis and metastasis. Therefore, tumor hypoxia with deregulated expression of HIF and its biological consequence lead to poor prognosis of patients diagnosed with solid tumors, resulting in higher mortality, suggesting that understanding of the molecular relationship of hypoxia with other cellular features of tumor aggressiveness would be invaluable for developing newer targeted therapy for solid tumors. It has been well recognized that cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) phenotypic cells are associated with therapeutic resistance and contribute to aggressive tumor growth, invasion, metastasis and believed to be the cause of tumor recurrence. Interestingly, hypoxia and HIF signaling pathway are known to play an important role in the regulation and sustenance of CSCs and EMT phenotype. However, the molecular relationship between HIF signaling pathway with the biology of CSCs and EMT remains unclear although NF-κB, PI3K/Akt/mTOR, Notch, Wnt/β-catenin, and Hedgehog signaling pathways have been recognized as important regulators of CSCs and EMT. In this article, we will discuss the state of our knowledge on the role of HIF-hypoxia signaling pathway and its kinship with CSCs and EMT within the tumor microenvironment. We will also discuss the potential role of hypoxia-induced microRNAs (miRNAs) in tumor development and aggressiveness, and finally discuss the potential effects of nutraceuticals on the biology of CSCs and EMT in the context of tumor hypoxia.

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Section: Hypoxia Hif and Treatment Resistance In Tumormentioning

confidence: 99%

The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness

Bao

Azmi

Ali

et al. 2012

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

128

139

View full text Add to dashboard Cite

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“…Genes regulating angiogenesis, proliferation, cancer stem cells (CSC), immune escape and metastasis can be induced, repressed or manipulated by the HIF transcription family 41. Intriguingly, several studies have found that over‐expression of HIF1α in human cancers represents a poor prognosis for tumor patients, in addition to its direct negative effect on cancer therapy 23, 42…”

Section: Hif In Cancermentioning

confidence: 99%

Hypoxia‐inducible factors as key regulators of tumor inflammation

Mamlouk¹,

Wielockx

2012

Intl Journal of Cancer

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Low levels of oxygen or hypoxia is often an obstacle in health, particularly in pathological disorders like cancer. The main family of transcription factors responsible for cell survival and adaptation under strenuous conditions of hypoxia are the ''hypoxia-inducible factors'' (HIFs). Together with prolyl hydroxylase domain enzymes (PHDs), HIFs regulates tumor angiogenesis, proliferation, invasion, metastasis, in addition to resistance to radiation and chemotherapy. Additionally, the entire HIF transcription cascade is involved in the ''seventh'' hallmark of cancer; inflammation. Studies have shown that hypoxia can influence tumor associated immune cells toward assisting in tumor proliferation, differentiation, vessel growth, distant metastasis and suppression of the immune response via cytokine expression alterations. These changes are not necessarily analogous to HIF's role in non-cancer immune responses, where hypoxia often encourages a strong inflammatory response.

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“…HIF is considered as an attractive drug target, and blocking of its activity might lead to cytostatic antitumour effects. A synergistic outcome with radiotherapy is also expected [33,34]. However, such drugs might be useful in multidrug regimes only in a subset of cancer patients.…”

Section: Clinical Aspectsmentioning

confidence: 99%

Hypoxic Upregulation of ARNT (HIF-1β): A Cell-Specific Attribute with Clinical Implications

Mandl¹,

Depping²

2017

Hypoxia and Human Diseases

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According to the current point of view described in the literature, the transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT), also designated as hypoxiainducible factor (HIF)-1β, is constitutively expressed and not influenced by oxygen tension. However, a study published two decades ago provided early evidence regarding a hypoxia-dependent ARNT upregulation. This finding was subsequently challenged and neglected. Until now, only a limited number of publications focus on the regulation of ARNT in hypoxia. Therefore, appropriate studies and the putative mechanism mediating this cellular attribute are discussed. The advantages of an elevated ARNT expression level in tumour cells are delineated. This chapter provides an overview of hypoxia-inducible ARNT as an emerging concept in HIF biology.

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Stabilisation and Knockdown of HIF - Two Distinct Ways Comparably Important in Radiotherapy

Cited by 16 publications

References 31 publications

The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness

The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness

Hypoxia‐inducible factors as key regulators of tumor inflammation

Hypoxic Upregulation of ARNT (HIF-1β): A Cell-Specific Attribute with Clinical Implications

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