Uridine Triphosphate Increases Proliferation of Human Cancerous Pancreatic Duct Epithelial Cells by Activating P2Y2 Receptor

Choi, Ji Hun; Ji, Young Geon; Lee, Dong Hyeon

doi:10.1097/mpa.0b013e318271bb4b

Cited by 29 publications

(25 citation statements)

References 40 publications

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“…Restoration of P2Y 2 R levels by lentiviral-mediated overexpression augments their proliferative and migratory capabilities (Figure 3). These results reinforce the emerging view of P2Y 2 R as pro-proliferative in various experimental models including hepatocytes 15, 44 , corneal endothelial cells 45 and pancreatic duct epithelial cells 46 . In addition, P2Y 2 R-induced migration in hCPCs is consistent with pro-migratory responses of P2Y 2 R in fibroblasts 24 , salivary 14 and corneal epithelial cells 13 .…”

Section: Discussionsupporting

confidence: 86%

P2Y ₂ Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling

Khalafalla

Greene

Khan

et al. 2017

Circulation Research

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Rationale Autologous stem cell therapy using human c-Kit+ cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged HF patients with genetic predispositions and/or comorbidities of chronic diseases exhibit poor proliferative and migratory capabilities, which impairs overall reparative potential for injured myocardium. Therefore, empowering functionally compromised hCPCs with pro-regenerative molecules ex vivo is crucial for improving the therapeutic outcome in HF patients. Objective To improve hCPC proliferation and migration responses that are critical for regeneration by targeting pro-regenerative P2Y2 nucleotide receptor (P2Y2R) activated by extracellular ATP and UTP molecules released following injury/stress. Methods and Results c-Kit+ hCPCs were isolated from cardiac tissue of HF patients undergoing left ventricular assist device (LVAD) implantation surgery. Correlations between P2 nucleotide receptor expression and hCPC growth kinetics revealed downregulation of select P2 receptors, including P2Y2R, in slow-growing hCPCs compared to fast-growers. hCPC proliferation and migration significantly improved by overexpressing or stimulating P2Y2R. Mechanistically, P2Y2R-induced proliferation and migration were dependent upon activation of yes-associated protein (YAP), the downstream effector of Hippo signaling pathway. Conclusions Proliferation and migration of functionally impaired hCPCs are enhanced by P2Y2R-mediated YAP activation, revealing a novel link between extracellular nucleotides released during injury/stress and Hippo signaling, a central regulator of cardiac regeneration. Functional correlations exist between hCPC phenotypic properties and P2 purinergic receptor expression. Lack of P2Y2R and other crucial purinergic stress detectors could compromise hCPC responsiveness to presence of extracellular stress signals. These findings set the stage for subsequent studies to assess purinergic signaling modulation as a potential strategy to improve therapeutic outcome for use of hCPCs in HF patients.

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Section: Discussionsupporting

confidence: 86%

P2Y ₂ Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling

Khalafalla

Greene

Khan

et al. 2017

Circulation Research

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“…18 Briefly, the siRNAs (Bioneer) against human SFKs (Src, Yes1, Lyn, Fyn, Hck, and Frk) were used. 18 Briefly, the siRNAs (Bioneer) against human SFKs (Src, Yes1, Lyn, Fyn, Hck, and Frk) were used.…”

Section: Sirna Inhibition Assaymentioning

confidence: 99%

The Inhibition of Src Family Kinase Suppresses Pancreatic Cancer Cell Proliferation, Migration, and Invasion

Je¹,

O²,

Ji³

et al. 2014

Pancreas

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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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Uridine Triphosphate Increases Proliferation of Human Cancerous Pancreatic Duct Epithelial Cells by Activating P2Y2 Receptor

Abstract: Uridine triphosphate increases proliferation of human pancreatic duct epithelial cells by activation of P2Y2 receptor and PI3K/Akt pathway. This could be helpful for discovering the long-term roles of P2Y2 receptor in pancreatic cells.

Cited by 29 publications

References 40 publications

P2Y ₂ Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling

P2Y ₂ Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling

The Inhibition of Src Family Kinase Suppresses Pancreatic Cancer Cell Proliferation, Migration, and Invasion

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

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Uridine Triphosphate Increases Proliferation of Human Cancerous Pancreatic Duct Epithelial Cells by Activating P2Y2 Receptor

Abstract: Uridine triphosphate increases proliferation of human pancreatic duct epithelial cells by activation of P2Y2 receptor and PI3K/Akt pathway. This could be helpful for discovering the long-term roles of P2Y2 receptor in pancreatic cells.

Cited by 29 publications

References 40 publications

P2Y 2 Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling

P2Y 2 Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling

The Inhibition of Src Family Kinase Suppresses Pancreatic Cancer Cell Proliferation, Migration, and Invasion

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

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P2Y ₂ Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling

P2Y ₂ Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling