scholarly journals From tumor hypoxia to cancer progression: the implications of hypoxia-inducible factor-1 expression in cancers

2012 ◽  
Vol 45 (2) ◽  
pp. 73 ◽  
Author(s):  
Fariz Nurwidya ◽  
Fumiyuki Takahashi ◽  
Kunihiko Minakata ◽  
Akiko Murakami ◽  
Kazuhisa Takahashi
Keyword(s):  
Cancer Progression ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Hypoxia Inducible Factor 1

TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Cancer Progression ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Human Lung Cancer ◽  
Regulatory Subunit ◽  
Patients With Cancer ◽  
Hypoxia Inducible Factor 1 ◽  
Chemically Induced ◽  
Induced Tumors ◽  
Patient Prognosis

Tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) activationare associated with cancer progression. Here, we demonstrate thatthe transcription factor TAp73 opposes HIF-1 activity through anontranscriptional mechanism, thus affecting tumor angiogenesis.TAp73-deficient mice have an increased incidence of spontaneousand chemically induced tumors that also display enhanced vascularization.Mechanistically, TAp73 interacts with the regulatory subunit(α) of HIF-1 and recruits mouse double minute 2 homolog intothe protein complex, thus promoting HIF-1α polyubiquitination andconsequent proteasomal degradation in an oxygen-independentmanner. In human lung cancer datasets, TAp73 strongly predictsgood patient prognosis, and its expression is associated with lowHIF-1 activation and angiogenesis. Our findings, supported by invivo and clinical evidence, demonstrate a mechanism for oxygenindependentHIF-1 regulation, which has important implicationsfor individualizing therapies in patients with cancer.

Anticancer Activity of Natural Flavonoids: Inhibition of HIF-1α Signaling Pathway

2020 ◽  
Vol 23 (26) ◽  
pp. 2945-2959 ◽  
Author(s):  
Xiangping Deng ◽  
Yijiao Peng ◽  
Jingduo Zhao ◽  
Xiaoyong Lei ◽  
Xing Zheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Pharmacological Activities ◽  
Hypoxia Inducible Factor 1 ◽  
The Past ◽  
Low Toxicity ◽  
Tumor Blood Vessels

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.

Abstract B7: Hypoxia-inducible factor 1 mediates thrombosis-associated cancer progression

2013 ◽  
Author(s):  
Colin E. Evans ◽  
Cristina Branco-Price ◽  
Julia Humphries ◽  
Ashar Wadoodi ◽  
Prakash Saha ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

LncIHAT is induced by hypoxia-inducible factor 1 and promotes breast cancer progression

2020 ◽  
pp. molcanres.0383.2020
Author(s):  
Lin Chen ◽  
Lei Bao ◽  
Yanling Niu ◽  
Jennifer E. Wang ◽  
Ashwani Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Hypoxia Inducible Factor ◽  
Breast Cancer Progression ◽  
Hypoxia Inducible Factor 1

scholarly journals Microenvironment and Radiation Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Michio Yoshimura ◽  
Satoshi Itasaka ◽  
Hiroshi Harada ◽  
Masahiro Hiraoka
Keyword(s):  
Radiation Therapy ◽  
Tumor Microenvironment ◽  
Antiangiogenic Therapy ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Tumor Oxygenation ◽  
Therapeutic Effects ◽  
Antitumor Effects ◽  
Hypoxia Inducible Factor 1 ◽  
Effects Of Radiation

Dependency on tumor oxygenation is one of the major features of radiation therapy and this has led many radiation biologists and oncologists to focus on tumor hypoxia. The first approach to overcome tumor hypoxia was to improve tumor oxygenation by increasing oxygen delivery and a subsequent approach was the use of radiosensitizers in combination with radiation therapy. Clinical use of some of these approaches was promising, but they are not widely used due to several limitations. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that is activated by hypoxia and induces the expression of various genes related to the adaptation of cellular metabolism to hypoxia, invasion and metastasis of cancer cells and angiogenesis, and so forth. HIF-1 is a potent target to enhance the therapeutic effects of radiation therapy. Another approach is antiangiogenic therapy. The combination with radiation therapy is promising, but several factors including surrogate markers, timing and duration, and so forth have to be optimized before introducing it into clinics. In this review, we examined how the tumor microenvironment influences the effects of radiation and how we can enhance the antitumor effects of radiation therapy by modifying the tumor microenvironment.

scholarly journals TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation

2014 ◽  
Vol 112 (1) ◽  
pp. 226-231 ◽  
Author(s):  
Ivano Amelio ◽  
Satoshi Inoue ◽  
Elke K. Markert ◽  
Arnold J. Levine ◽  
Richard A. Knight ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Tumor Angiogenesis ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Human Lung Cancer ◽  
Regulatory Subunit ◽  
Independent Manner ◽  
Induced Tumors ◽  
Patient Prognosis

Tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) activation are associated with cancer progression. Here, we demonstrate that the transcription factor TAp73 opposes HIF-1 activity through a nontranscriptional mechanism, thus affecting tumor angiogenesis. TAp73-deficient mice have an increased incidence of spontaneous and chemically induced tumors that also display enhanced vascularization. Mechanistically, TAp73 interacts with the regulatory subunit (α) of HIF-1 and recruits mouse double minute 2 homolog into the protein complex, thus promoting HIF-1α polyubiquitination and consequent proteasomal degradation in an oxygen-independent manner. In human lung cancer datasets, TAp73 strongly predicts good patient prognosis, and its expression is associated with low HIF-1 activation and angiogenesis. Our findings, supported by in vivo and clinical evidence, demonstrate a mechanism for oxygen-independent HIF-1 regulation, which has important implications for individualizing therapies in patients with cancer.

scholarly journals Hypoxia-dependent drivers of melanoma progression

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Simona D’Aguanno ◽  
Fabiana Mallone ◽  
Marco Marenco ◽  
Donatella Del Bufalo ◽  
Antonietta Moramarco
Keyword(s):  
Cancer Progression ◽  
Current Knowledge ◽  
Hypoxia Inducible Factor ◽  
Vasculogenic Mimicry ◽  
Mucosal Melanoma ◽  
Response To Therapy ◽  
Molecular Profile ◽  
Low Oxygen ◽  
Hypoxia Inducible Factor 1 ◽  
Melanoma Progression

AbstractHypoxia, a condition of low oxygen availability, is a hallmark of tumour microenvironment and promotes cancer progression and resistance to therapy. Many studies reported the essential role of hypoxia in regulating invasiveness, angiogenesis, vasculogenic mimicry and response to therapy in melanoma. Melanoma is an aggressive cancer originating from melanocytes located in the skin (cutaneous melanoma), in the uveal tract of the eye (uveal melanoma) or in mucosal membranes (mucosal melanoma). These three subtypes of melanoma represent distinct neoplasms in terms of biology, epidemiology, aetiology, molecular profile and clinical features.In this review, the latest progress in hypoxia-regulated pathways involved in the development and progression of all melanoma subtypes were discussed. We also summarized current knowledge on preclinical studies with drugs targeting Hypoxia-Inducible Factor-1, angiogenesis or vasculogenic mimicry. Finally, we described available evidence on clinical studies investigating the use of Hypoxia-Inducible Factor-1 inhibitors or antiangiogenic drugs, alone or in combination with other strategies, in metastatic and adjuvant settings of cutaneous, uveal and mucosal melanoma.Hypoxia-Inducible Factor-independent pathways have been also reported to regulate melanoma progression, but this issue is beyond the scope of this review.As evident from the numerous studies discussed in this review, the increasing knowledge of hypoxia-regulated pathways in melanoma progression and the promising results obtained from novel antiangiogenic therapies, could offer new perspectives in clinical practice in order to improve survival outcomes of melanoma patients.

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