Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells

Eskandani, Morteza; Vandghanooni, Somayeh; Barar, Jaleh; Nazemiyeh, Hossein; Omidi, Yadollah

doi:10.1016/j.ijbiomac.2016.10.113

Cited by 34 publications

(27 citation statements)

References 192 publications

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“…In healthy people, variations in oxygen concentration show a critical regulatory effect on metabolism, proliferation and differentiation of cells [16]. To adapt to the stress responses to hypoxic metabolism, tumor cells could activate a series of signaling pathways, including the pathways promoting the peripheral angiogenesis, enhancing cell metabolism and migration, or facilitating the abnormal proliferation, metastasis and drug resistance [17,18].…”

Section: Discussionmentioning

confidence: 99%

Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/ÃÂ²-catenin signaling pathway

Ma¹,

He²,

Wang³

et al. 2018

biomedicalresearch

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Objective: To study the effect of Wnt/β-catenin signaling pathway on hypoxia induced proliferation and invasion in lung cancer cell line A549. Methods: Cultured lung cancer A549 cells were treated with hypoxia for 24 h. The proliferation rates were detected by CCK8; the mRNA and protein expression levels of HIF-1α and β-catenin were detected by RT-PCR and Western blot; the effect of hypoxia on invasion ability of A549 cells were detected with Transwell method. Furthermore, β-catenin siRNA was used to investigate the role of β-catenin on hypoxia induced proliferation and invasion. Results: The results demonstrated that hypoxia could promote A549 cells proliferation and invasion. The mRNA and protein level of HIF-1α and β-catenin was upregulated by hypoxia treatment, whereas β-catenin siRNA could block these processes. Conclusion: Hypoxia promotes osteosarcoma cell line A549 proliferation and invasion by activating Wnt/β-catenin signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/ÃÂ²-catenin signaling pathway

Ma¹,

He²,

Wang³

et al. 2018

biomedicalresearch

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“…HIF‐1β is constitutively expressed, whereas HIF‐1α is an oxygen‐sensitive subunit, and its expression is induced under hypoxic conditions (Masoud & Lin, ; Eskandani et al. ). HIF‐1α is constitutively transcribed and synthesized through a series of signalling events that involve several growth factors and other signalling molecules (Masoud & Lin, ).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, HIF-1 is a heterodimeric transcription factor that is composed of two subunits: HIF-1a (or its analogues HIF-2a and HIF-3a) and HIF-1b subunits. HIF-1b is constitutively expressed, whereas HIF-1a is an oxygen-sensitive subunit, and its expression is induced under hypoxic conditions (Masoud & Lin, 2015;Eskandani et al 2017). HIF-1a is constitutively transcribed and synthesized through a series of signalling events that involve several growth factors and other signalling molecules (Masoud & Lin, 2015).…”

Section: Introductionmentioning

confidence: 99%

HIF1α protein and mRNA expression as a new marker for post mortem interval estimation in human gingival tissue

et al. 2018

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Estimating the post mortem interval (PMI) is still a crucial step in Forensic Pathology. Although several methods are available for assessing the PMI, a precise estimation is still quite unreliable and can be inaccurate. The present study aimed to investigate the immunohistochemical distribution and mRNA expression of hypoxia inducible factor (HIF‐1α) in post mortem gingival tissues to establish a correlation between the presence of HIF‐1α and the time since death, with the final goal of achieving a more accurate PMI estimation. Samples of gingival tissues were obtained from 10 cadavers at different PMIs (1–3 days, 4–5 days and 8–9 days), and were processed for immunohistochemistry and quantitative reverse transcription‐polymerase chain reaction. The results showed a time‐dependent correlation of HIF‐1α protein and its mRNA with different times since death, which suggests that HIF‐1α is a potential marker for PMI estimation. The results showed a high HIF‐1α protein signal that was mainly localized in the stratum basale of the oral mucosa in samples collected at a short PMI (1–3 days). It gradually decreased in samples collected at a medium PMI (4–5 days), but it was not detected in samples collected at a long PMI (8–9 days). These results are in agreement with the mRNA data. These data indicate an interesting potential utility of Forensic Anatomy‐based techniques, such as immunohistochemistry, as important complementary tools to be used in forensic investigations.

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“…52 Under hypoxia tumor condition, hypoxia-inducible factors (HIFs) as a transcription factor was shown to elicit the expression of several genes involved in the survival and angiogenesis of solid tumor. 53,56 Tumor hypoxia conditions can also disrupt the protein foldings in the endoplasmic reticulum, 57 which may favor cancer cells in attaining drug-resistance by targeting elements such astopoisomerase ΙΙ. 58 The traits of TME such as irregularly non-integrated tumor microvasculature, highly pressurized tumor interstitial fluid, and dysregulated pH appear to be involved in drug-resistance properties of cancer cells.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

“…Such phenomena result in the functional expression of the hypoxia responsive elements (HREs) such as glucose transporters (GLUT-1 and GLUT-3), vascular endothelial growth factor (VEGF) and CAIX. 56,134,144 Of these, CAIX contributes to the acidification of TME. It may also lead to the phenotype of metastasis.…”

Section: Carbonic Anhydrasesmentioning

confidence: 99%

Molecular machineries of pH dysregulation in tumor microenvironment: potential targets for cancer therapy

Asgharzadeh¹,

Barar²,

Pourseif³

et al. 2017

Bioimpacts

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106

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Introduction: Cancer is an intricate disorder/dysfunction of cells that can be defined as a genetic heterogeneity in human disease. Therefore, it is characterized by several adaptive complex hallmarks. Among them, the pH dysregulation appears as a symbol of aberrant functions within the tumor microenvironment (TME). In comparison with normal tissues, in the solid tumors, we face with an irregular acidification and alkalinization of the extracellular and intracellular fluids. Methods: In this study, we comprehensively discussed the most recent reports on the hallmarks of solid tumors to provide deep insights upon the molecular machineries involved in the pH dysregulation of solid tumors and their impacts on the initiation and progression of cancer. Results: The dysregulation of pH in solid tumors is fundamentally related to the Warburg effect and hypoxia, leading to expression of a number of molecular machineries, including: NHE1, H+ pump V-ATPase, CA-9, CA-12, MCT-1, GLUT-1. Activation of proton exchangers and transporters (PETs) gives rise to formation of TME. This condition favors the cancer cells to evade from the anoikis and apoptosis, granting them aggressive and metastasis phenotype, as well as resistance to chemotherapy and radiation therapy. This review aimed to discuss the key molecular changes of tumor cells in terms of bio-energetics and cancer metabolism in relation with pH dysregulation. During this phenomenon, the intra- and extracellular metabolites are altered and/or disrupted. Such molecular alterations provide molecular hallmarks for direct targeting of the PETs by potent relevant inhibitors in combination with conventional cancer therapies as ultimate therapy against solid tumors. Conclusion: Taken all, along with other treatment strategies, targeting the key molecular machineries related to intra- and extracellular metabolisms within the TME is proposed as a novel strategy to inhibit or block PETs that are involved in the pH dysregulation of solid tumors.

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Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells

Cited by 34 publications

References 192 publications

Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/ÃÂ²-catenin signaling pathway

Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/ÃÂ²-catenin signaling pathway

HIF1α protein and mRNA expression as a new marker for post mortem interval estimation in human gingival tissue

Molecular machineries of pH dysregulation in tumor microenvironment: potential targets for cancer therapy

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Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells

Cited by 34 publications

References 192 publications

Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/ÃÂ²-catenin signaling pathway

Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/ÃÂ²-catenin signaling pathway

HIF1α protein and mRNA expression as a new marker for post mortem interval estimation in human gingival tissue

Molecular machineries of pH dysregulation in tumor microenvironment: potential targets for cancer therapy

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Product

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Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/ÃÂ²-catenin signaling pathway

Hypoxic microenvironment promotes proliferation and invasion of non-small cell lung cancer A549 Cells through Wnt/ÃÂ²-catenin signaling pathway