The activation of P2Y2 receptors increases MCF-7 breast cancer cells migration through the MEK-ERK1/2 signalling pathway.

Abstract

Adenosine 5'-triphosphate (ATP) is found in high concentrations in the extracellular microenvironment of tumours and is postulated to play critical roles in cancer progression. In the present study, we found that stimulation of human MCF-7 breast cancer cells with 30 µM ATP increased their migration by 140 ± 31%, whereas it had minor or no effect on their proliferation. This effect was prevented by the ectonucleotidase apyrase and was antagonized by suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, consistently with the participation of P2 receptors. MCF-7 cells expressed messenger RNA for all known P2Y receptors and for P2X2, P2X4, P2X5, P2X6 and P2X7 receptors. Brief applications (20 s) of external ATP resulted in a 50 pA P2X-like inward current. ATP, but not adenosine diphosphate or uridine diphosphate, increased the intracellular calcium concentration in absence of extracellular calcium, and this effect was prevented by the inhibition of phospholipase C. Uridine triphosphate (UTP) (10 µM) and 2-thio-UTP (10 µM) increased intracellular calcium concentration and cell migration to the same extent as ATP. The UTP-dependent increase in cell migration was absent in cells knocked-down for P2Y2. It was inhibited by MEK inhibitor PD98059. UTP induced a time-dependent phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), which was prevented by the incubation with PD98059. Taken together, these results highlight the importance of the purinergic signalling in cancer cells and indicate that the activation of P2Y2 receptors enhances breast cancer cells migration through the activation of a MEK-ERK1/2-dependent signalling pathway.

• Authors: Stéphanie Chadet, Bilel Jelassi, Ramez Wannous, Denis Angoulvant, Stéphan Chevalier, Pierre Besson, Sébastien Roger
• Journal: Carcinogenesis (Carcinogenesis) Vol. 35 Issue 6 Pg. 1238-47 (Jun 2014) ISSN: 1460-2180 [Electronic] England
• PMID: 24390819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Receptors, Purinergic P2Y2
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism, pharmacology)
• Breast Neoplasms (genetics, metabolism)
• Cell Movement (drug effects, genetics)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Female
• Gene Expression
• Humans
• MAP Kinase Signaling System
• MCF-7 Cells
• RNA Interference
• Receptors, Purinergic P2Y2 (genetics, metabolism)