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.

scholarly journals SEMAPHORINS and their receptors: focus on the crosstalk between melanoma and hypoxia

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Elisabetta Valentini ◽  
Marta Di Martile ◽  
Donatella Del Bufalo ◽  
Simona D’Aguanno
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Hypoxia Inducible Factor ◽  
Cell Communication ◽  
Hypoxic Condition ◽  
Response To Therapy ◽  
Hypoxia Inducible Factor 1 ◽  
Shed Light

AbstractHypoxia, a condition of oxygen deprivation, is considered a hallmark of tumor microenvironment regulating several pathways and promoting cancer progression and resistance to therapy. Semaphorins, a family of about 20 secreted, transmembrane and GPI-linked glycoproteins, and their cognate receptors (plexins and neuropilins) play a pivotal role in the crosstalk between cancer and stromal cells present in the tumor microenvironment. Many studies reported that some semaphorins are involved in the development of a permissive tumor niche, guiding cell-cell communication and, consequently, the development and progression, as well as the response to therapy, of different cancer histotypes, including melanoma.In this review we will summarize the state of art of semaphorins regulation by hypoxic condition in cancer with different origin. We will also describe evidence about the ability of semaphorins to affect the expression and activity of transcription factors activated by hypoxia, such as hypoxia-inducible factor-1. Finally, we will focus our attention on findings reporting the role of semaphorins in melanocytes transformation, melanoma progression and response to therapy. Further studies are necessary to understand the mechanisms through which semaphorins induce their effect and to shed light on the possibility to use semaphorins or their cognate receptors as prognostic markers and/or therapeutic targets in melanoma or other malignancies.

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.

scholarly journals Evodiamine inhibits vasculogenic mimicry in HCT116 cells by suppressing hypoxia-inducible factor 1-alpha-mediated angiogenesis

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Di Zeng ◽  
Peng Zhou ◽  
Rong Jiang ◽  
Xiao-peng Li ◽  
Shi-ying Huang ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Vasculogenic Mimicry ◽  
Hypoxia Inducible Factor 1 ◽  
Hct116 Cells

scholarly journals Hypoxia and Oxygen-Sensing Signaling in Gene Regulation and Cancer Progression

2020 ◽  
Vol 21 (21) ◽  
pp. 8162
Author(s):  
Guang Yang ◽  
Rachel Shi ◽  
Qing Zhang
Keyword(s):  
Gene Regulation ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylases ◽  
Von Hippel Lindau ◽  
Oxygen Homeostasis ◽  
Jmjc Domain ◽  
Encoding Protein

Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression. The key molecules of the hypoxia/oxygen-sensing signaling include the transcriptional regulator hypoxia-inducible factor (HIF) which widely controls oxygen responsive genes, the central members of the 2-oxoglutarate (2-OG)-dependent dioxygenases, such as prolyl hydroxylase (PHD or EglN), and an E3 ubiquitin ligase component for HIF degeneration called von Hippel–Lindau (encoding protein pVHL). In this review, we summarize the current knowledge about the canonical hypoxia signaling, HIF transcription factors, and pVHL. In addition, the role of 2-OG-dependent enzymes, such as DNA/RNA-modifying enzymes, JmjC domain-containing enzymes, and prolyl hydroxylases, in gene regulation of cancer progression, is specifically reviewed. We also discuss the therapeutic advancement of targeting hypoxia and oxygen sensing pathways in cancer.

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 Regeneration in Spinal Disease: Therapeutic Role of Hypoxia-Inducible Factor-1 Alpha in Regeneration of Degenerative Intervertebral Disc

2021 ◽  
Vol 22 (10) ◽  
pp. 5281
Author(s):  
Jin-Woo Kim ◽  
Neunghan Jeon ◽  
Dong-Eun Shin ◽  
So-Young Lee ◽  
Myongwhan Kim ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Structural Changes ◽  
Hypoxia Inducible Factor ◽  
Low Oxygen ◽  
Hypoxia Inducible Factor 1 ◽  
Metabolic Activities ◽  
Cartilaginous Endplate ◽  
Ivd Degeneration ◽  
Complex Joint

The intervertebral disc (IVD) is a complex joint structure comprising three primary components—namely, nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP). The IVD retrieves oxygen from the surrounding vertebral body through CEP by diffusion and likely generates ATP via anaerobic glycolysis. IVD degeneration is characterized by a cascade of cellular, compositional, structural changes. With advanced age, pronounced changes occur in the composition of the disc extracellular matrix (ECM). NP and AF cells in the IVD possess poor regenerative capacity compared with that of other tissues. Hypoxia-inducible factor (HIF) is a master transcription factor that initiates a coordinated cellular cascade in response to a low oxygen tension environment, including the regulation of numerous enzymes in response to hypoxia. HIF-1α is essential for NP development and homeostasis and is involved in various processes of IVD degeneration process, promotes ECM in NP, maintains the metabolic activities of NP, and regulates dystrophic mineralization of NP, as well as angiogenesis, autophagy, and apoptosis during IVD degeneration. HIF-1α may, therefore, represent a diagnostic tool for early IVD degeneration and a therapeutic target for inhibiting IVD degeneration.

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