Dual role of HIF‐1α in delivering a survival or death signal in hypoxia exposed human K562 erythroleukemia cells

Giacomo, Viviana di; Rapino, Monica; Miscia, Sebastianó; Giulio, Camillo Di; Cataldi, Amelia

doi:10.1016/j.cellbi.2008.10.014

Cited by 6 publications

(5 citation statements)

References 40 publications

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“…In favor of this hypothesis, intermittent hypoxia increases survival of APL mice ( 123 ). Similarly, in CML, HIF-1alpha induction following short (5 h) hypoxia exposure delivered a survival signal to cells, whereas it promoted cell death within a longer period (22 h) ( 127 ). In the ALL model, 24 h-exposure to hypoxia conferred chemoresistance in contrast to longer exposure (48–72 h) ( 128 ).…”

Section: Hypoxia-inducible Factors In Leukemiasmentioning

confidence: 99%

Hypoxia and Hypoxia-Inducible Factors in Leukemias

et al. 2016

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Despite huge improvements in the treatment of leukemia, the percentage of patients suffering relapse still remains significant. Relapse most often results from a small number of leukemic stem cells (LSCs) within the bone marrow, which are able to self-renew, and therefore reestablish the full tumor. The marrow microenvironment contributes considerably in supporting the protection and development of leukemic cells. LSCs share specific niches with normal hematopoietic stem cells with the niche itself being composed of a variety of cell types, including mesenchymal stem/stromal cells, bone cells, immune cells, neuronal cells, and vascular cells. A hallmark of the hematopoietic niche is low oxygen partial pressure, indeed this hypoxia is necessary for the long-term maintenance of hematopoietic stem/progenitor cells. Hypoxia is a strong signal, principally maintained by members of the hypoxia-inducible factor (HIF) family. In solid tumors, it has been well established that hypoxia triggers intrinsic metabolic changes and microenvironmental modifications, such as the stimulation of angiogenesis, through activation of HIFs. As leukemia is not considered a “solid” tumor, the role of oxygen in the disease was presumed to be inconsequential and remained long overlooked. This view has now been revised since hypoxia has been shown to influence leukemic cell proliferation, differentiation, and resistance to chemotherapy. However, the role of HIF proteins remains controversial with HIFs being considered as either oncogenes or tumor suppressor genes, depending on the study and model. The purpose of this review is to highlight our knowledge of hypoxia and HIFs in leukemic development and therapeutic resistance and to discuss the recent hypoxia-based strategies proposed to eradicate leukemias.

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Section: Hypoxia-inducible Factors In Leukemiasmentioning

confidence: 99%

Hypoxia and Hypoxia-Inducible Factors in Leukemias

et al. 2016

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“…PKC is also involved in IFN--induced growth inhibition of CML cells through phosphorylation of Stat1 [374]. On the other hand, PKC may also participate in K562 cell death because of a close relationship between activation of the PKC /ERK pathway and high levels of Bax at hypoxia-induced apoptosis [375].…”

Section: And Amlmentioning

confidence: 99%

Protein Kinase C (PKC) Isozymes and Cancer

Kang

2014

New Journal of Science

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Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine kinases, which can be further classified into three PKC isozymes subfamilies: conventional or classic, novel or nonclassic, and atypical. PKC isozymes are known to be involved in cell proliferation, survival, invasion, migration, apoptosis, angiogenesis, and drug resistance. Because of their key roles in cell signaling, PKC isozymes also have the potential to be promising therapeutic targets for several diseases, such as cardiovascular diseases, immune and inflammatory diseases, neurological diseases, metabolic disorders, and multiple types of cancer. This review primarily focuses on the activation, mechanism, and function of PKC isozymes during cancer development and progression.

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“…A study of 2009 reported that human leukemia K562 cells show a down regulation of proliferation and an increase of cell death after 22 hours of hypoxia. While 5 hours of hypoxia were able to increase HIF-1 expression, but did not modify cell cycle progression or affect cell death [29].…”

Section: Tumor Hypoxiamentioning

confidence: 99%

Role of the Hypoxic Microenvironment in the Antitumor Activity of Tyrosine Kinase Inhibitors

Filippi

Naldini²,

Carraro³

2011

CMC

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The tumor microenvironment is characterized, not only by marked gradients in drug concentration, but also by gradients in the rate of cell proliferation and by regions of hypoxia and acidity, all of which can influence tumor cell sensitivity to drug treatment. Hypoxia is also an important environmental factor in chronic myeloid leukemia (CML), because bone marrow is intrinsically hypoxic in nature. Systems-wide analyses of tumors have recently identified receptor tyrosine kinase coactivation as an important mechanism by which cancer cells achieve chemoresistance. Recent work suggests that Src activation might play a prominent role in the response to hypoxia to promote cell survival, progression, and metastasis of a variety of human cancer. Other studies also established a functional link between Bcr-Abl and the Src family tyrosine kinases. It is well known that mutations can also cause some tyrosine kinases to become constitutively active, a nonstop functional state that may contribute to initiation or progression of cancer as in CML. Leukemic cells carrying chromosomal alteration, are sensitive to imatinib that induces complete remission in most patients. This inhibitor is a highly selective Bcr-Abl tyrosine kinase inhibitor (TKI). There is a considerable interest in understanding how activated signaling pathways enhance tumor cell survival under hypoxia, because this might lead to the introduction of more effective treatments to target these resistant subpopulations. For all these reasons it is important to identify new TKIs which are also active in hypoxia, the real tumor microenvironment, as possible alternative therapy.

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Dual role of HIF‐1α in delivering a survival or death signal in hypoxia exposed human K562 erythroleukemia cells

Cited by 6 publications

References 40 publications

Hypoxia and Hypoxia-Inducible Factors in Leukemias

Hypoxia and Hypoxia-Inducible Factors in Leukemias

Protein Kinase C (PKC) Isozymes and Cancer

Role of the Hypoxic Microenvironment in the Antitumor Activity of Tyrosine Kinase Inhibitors

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