P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells

Wh, Li; Qiu, Yue; Hq, Zhang; Y, Liu; Jf, You; Tian, Xiaofeng; Wg, Fang

doi:10.1038/bjc.2013.484

Cited by 103 publications

(118 citation statements)

References 43 publications

(52 reference statements)

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“…For instance, in two prostate cancer (PC) cell lines derived from PC-3cells, stimulationof one typeof P2Y receptor with ATP induced an increase in their migratory and invasive abilities, an action mediated by the activation of kinases ERK and p38 [86]. Eventually, P2Y2 was identified as one of the receptors responsible for the ATP-induced invasive response of the PC cells; the process involved the activation of the EMT program, since expression of the transcripts coding for Snail and IL-8 increased whereas those for E-cadherin and claudin decreased [87]. Further analysis of the molecular mechanism showed that P2Y2 receptor activation during EMTwas associated with EGFR activity.…”

Section: Purinergic Signaling Emt and Invasivenessmentioning

confidence: 99%

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Martinez-Ramirez

Dı́az-Muñoz

Butanda-Ochoa

et al. 2016

Purinergic Signalling

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The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities. In this context, cellular signaling associated to purines is opening the understanding of a new element in the complex regulatory network of this phenotypical differentiation process. In this review, we have summarized recent information about the role of ATP and adenosine in EMT, as a growing field with high therapeutic potential.Keywords P2 receptors . P1 receptors . Purinergic signaling . Cell migration . EMTThe purinergic system of intercellular communication General aspects The term purine (from: pure urine) was created more than 130 years ago by Emil Fischer after detailed analytical characterization of the uric acid molecule [1]. Purine molecular structure is the result of fusing pyrimidine and imidazole rings, and it exists as four N-H tautomeric forms [2]. Tautomerism of purine bases in DNA is one of the earliest reasons for mutations [3][4][5]. The interconversion of the different adenine or guanine tautomers produced mispairing with pyrimidines (which also show tautomeric forms) that may lead to changes in DNA sequence [6].Purine molecules appeared very early in the history of our planet, in the period known as Borganic evolution^, before the establishment of living systems. It has been postulated that purines could be formed by a eutectic (denoting a mixture of substances in fixed proportions that melts and freezes at a single temperature that is lower than the melting points of any of the separate constituents) concentration of HCN at extremely low temperature over a period of dozens of years [7]. Purine molecules, such as adenine and guanine, are components of the genetic material (DNA and RNA) of all living beings. Purine and pyrimidine tautomeric equilibria in nucleic acids was postulated to be significant in events such as DNA replication and repair as well as in the occurrence of point mutations [8].As nucleosides and nucleotides, purines play other highly strategic roles, acting as energy intermediates, allosteric regulators of key metabolic activities, redox molecules, and chemical messengers for signal transduction events. The two most important purines serving as extracellular ligands for paracrine and autocrine signaling are ATP and its dephosphorylated form, adenosine (ADO). ATP and ADO act as intracellular intermediate metabolites, and their presence in the

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Section: Purinergic Signaling Emt and Invasivenessmentioning

confidence: 99%

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Martinez-Ramirez

Dı́az-Muñoz

Butanda-Ochoa

et al. 2016

Purinergic Signalling

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“…S1D). Among other requirements, the ability of tumor cells to migrate and invade adjacent structures depends on cellular energy production (21,22). To test whether altered PHD3 expression affected ATP production in tumor cells, we performed ATP assays under varying conditions.…”

Section: Phd3 Expression Affects Mitochondrial Atp Production Of Tumomentioning

confidence: 99%

Prolyl Hydroxylase 3 Attenuates MCL-1–Mediated ATP Production to Suppress the Metastatic Potential of Colorectal Cancer Cells

et al. 2016

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Hypoxia is a common feature of solid tumors. Prolyl hydroxylase enzymes (PHD1-3) are molecular oxygen sensors that regulate hypoxia-inducible factor activity, but their functions in metastatic disease remain unclear. Here, we assessed the significance of PHD enzymes during the metastatic spread of colorectal cancer. PHD expression analysis in 124 colorectal cancer patients revealed that reduced tumoral expression of PHD3 correlated with increased frequency of distant metastases and poor outcome. Tumorigenicity and metastatic potential of colorectal tumor cells over and underexpressing PHD3 were investigated in orthotopic and heterotopic tumor models. PHD3 overexpression in a syngeneic tumor model resulted in fewer liver metastases, whereas PHD3 knockdown induced tumor spread. The migration of PHD3-overexpressing tumor cells was also attenuated in vitro. Conversely, migratory potential and colony formation were enhanced in PHD3-deficient cells, and this phenotype was associated with enhanced mitochondrial ATP production. Furthermore, the effects of PHD3 deficiency were accompanied by increased mitochondrial expression of the BCL-2 family member, member myeloid cell leukemia sequence 1 (MCL-1), and could be reversed by simultaneous inhibition of MCL-1. MCL-1 protein expression was likewise enhanced in human colorectal tumors expressing low levels of PHD3. Therefore, we demonstrate that downregulation of PHD3 augments metastatic spread in human colorectal cancer and identify MCL-1 as a novel downstream effector of oxygen sensing. Importantly, these findings offer new insight into the possible, context-specific deleterious effects of pharmacologic PHD inhibition. Cancer Res; 76(8); 2219-30. Ó2016 AACR.

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“…P2Y2 receptor recognizes ATP and UTP ligands, and bind G-protein by phospholipase C (PLC) activation and mobilizing intracellular Ca 2+ (Li et al, 2011). This receptor subtype is involved in proliferation of certain tumors including lung (Schumacher et al, 2013), pancreas (Choi et al, 2013), prostate (Li et al, 2013) and breast (Li et al, 2011). In contrast, in colorectal cancer, this receptor blocks cell proliferation (Küntzli et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of P2RY2, CD248 and EphB1 in Gastric Cancers from Chilean Patients

Aquea

Bresky²,

Lancellotti³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells

Cited by 103 publications

References 43 publications

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Prolyl Hydroxylase 3 Attenuates MCL-1–Mediated ATP Production to Suppress the Metastatic Potential of Colorectal Cancer Cells

Increased Expression of P2RY2, CD248 and EphB1 in Gastric Cancers from Chilean Patients

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