PI3K/Akt-mediated regulation of p53 in cancer

Abraham, Aswin George; O’Neill, Eric

doi:10.1042/bst20140070

Cited by 174 publications

(127 citation statements)

References 78 publications

(83 reference statements)

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“…Additionally Akt activates FOXO3a to inhibit apoptosis and increase mitochondrial biogenesis to support a growing cell [23]. The PI3K/Akt signaling pathway is essential for normal cellular function, and commonly this pathway is mutated and hyperactivated in cancer models [24]. Thus activation of Akt triggers increase in cell size, enhanced glycolytic activity and metabolism, as well as cell survival [25].…”

Section: The Debate Regarding the Initiating Events Of Cancermentioning

confidence: 98%

“…This evidence suggests that the genetic dysfunction that is found in cancer cells is causatively due from a secondary consequence to mitochondrial dysfunction. p53 and cancer p53 is a cellular regulator and transcriptional factor with tumour suppressor properties which is an important regulator of cell death and replicative senescence in response to oncogenic stress [24]. It is often described as the 'guardian of the genome'.…”

Section: The Debate Regarding the Initiating Events Of Cancermentioning

confidence: 99%

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Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K

et al. 2015

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Cancer cells have been shown to have altered metabolism when compared to normal non-malignant cells. The Warburg effect describes a phenomenon in which cancer cells preferentially metabolize glucose by glycolysis, producing lactate as an end product, despite being the presence of oxygen. The phenomenon was first described by Otto Warburg in the 1920s, and has resurfaced as a controversial theory, with both supportive and opposing arguments. The biochemical aspects of the Warburg effect outline a strong explanation for the cause of cancer cell proliferation, by providing the biological requirements for a cell to grow. Studies have shown that pathways such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) as well as hypoxia inducible factor-1 (HIF-1) are central regulators of glycolysis, cancer metabolism and cancer cell proliferation. Studies have shown that PI3K signaling pathways have a role in many cellular processes such as metabolism, inflammation, cell survival, motility and cancer progression. Herein, the cellular aspects of the PI3K pathway are described, as well as the influence HIF has on cancer cell metabolism. HIF-1 activation has been related to angiogenesis, erythropoiesis and modulation of key enzymes involved in aerobic glycolysis, thereby modulating key processes required for the Warburg effect. In this review we discuss the molecular aspects of the Warburg effect with a particular emphasis on the role of the HIF-1 and the PI3K pathway.

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Section: The Debate Regarding the Initiating Events Of Cancermentioning

confidence: 98%

Section: The Debate Regarding the Initiating Events Of Cancermentioning

confidence: 99%

Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K

et al. 2015

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“…The increased potential for cellular proliferation leading towards tumorigenesis initiated through PKB activation may also result from a response towards various cellular stimuli, such as heat shock, osmotic, and oxidative stress [229]. Mechanistic research has revealed a wide range of influences [231], including critical roles by AKT in proliferation [232], resistance to apoptosis [233], glucose metabolism [234], cell migration, [235] and the regulation of autophagy [236]. …”

Section: Therapeutic Targetsmentioning

confidence: 99%

A multi-targeted approach to suppress tumor-promoting inflammation

Samadi

Bilsland

Georgakilas

et al. 2015

Seminars in Cancer Biology

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Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.

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“…S8a). AKT1 is a member of AKT signaling and it is known that active AKT signaling mediates degradation of the tumor suppressor TP53 (Abraham et al , 2014). Hence, overexpression of AKT1 could be the cause of TP53 downregulation.…”

Section: Resultsmentioning

confidence: 99%

Network-based integration of multi-omics data for prioritizing cancer genes

et al. 2018

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MotivationSeveral molecular events are known to be cancer-related, including genomic aberrations, hypermethylation of gene promoter regions and differential expression of microRNAs. These aberration events are very heterogeneous across tumors and it is poorly understood how they affect the molecular makeup of the cell, including the transcriptome and proteome. Protein interaction networks can help decode the functional relationship between aberration events and changes in gene and protein expression.ResultsWe developed NetICS (Network-based Integration of Multi-omics Data), a new graph diffusion-based method for prioritizing cancer genes by integrating diverse molecular data types on a directed functional interaction network. NetICS prioritizes genes by their mediator effect, defined as the proximity of the gene to upstream aberration events and to downstream differentially expressed genes and proteins in an interaction network. Genes are prioritized for individual samples separately and integrated using a robust rank aggregation technique. NetICS provides a comprehensive computational framework that can aid in explaining the heterogeneity of aberration events by their functional convergence to common differentially expressed genes and proteins. We demonstrate NetICS’ competitive performance in predicting known cancer genes and in generating robust gene lists using TCGA data from five cancer types.Availability and implementationNetICS is available at https://github.com/cbg-ethz/netics.Supplementary information Supplementary data are available at Bioinformatics online.

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PI3K/Akt-mediated regulation of p53 in cancer

Cited by 174 publications

References 78 publications

Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K

Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K

A multi-targeted approach to suppress tumor-promoting inflammation

Network-based integration of multi-omics data for prioritizing cancer genes

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