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P2Y2 Receptor Functions in Cancer: A Perspective in the Context of Colorectal Cancer

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  • First Online:
Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 1051))

Abstract

Purinergic signaling has recently emerged as a network of signaling molecules, enzymes and receptors that coordinates the action and behavior of cancerous cells. Extracellular adenosine 5′ triphosphate activates a plethora of P2 nucleotide receptors that can putatively modulate cancer cell proliferation, survival and dissemination. In this context, the G protein-coupled P2Y2 receptor was identified as one of the entities coordinating the cellular and molecular events that characterize cancerous cells. In this chapter, we will look at the contribution of the P2Y2 receptor in cancer outcomes and use this information to demonstrate that the P2Y2 receptor represents a drug target of interest in the setting of colorectal cancer, for which the role and function of this receptor is poorly defined. More particularly, we will review how the P2Y2 receptor modulates cancer cell proliferation and survival, while promoting cell dissemination and formation of metastases. Finally, we will investigate how the P2Y2 receptor can contribute to the detrimental development of drug resistance that is often observed in cancerous cells.

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Abbreviations

AOM:

Azoxymethane

APC:

Adenomatous polyposis coli

ATP:

Adenosine 5′-triphosphate

BMDC:

Bone marrow-derived dendritic cell

C/EBPβ:

CCAAT-enhancer-binding protein beta

CRC:

Colorectal cancer

DSS:

Dextran sulfate sodium

EGF:

Epithelial growth factor

EMT:

Epithelial-mesenchymal transition

GPCR:

G protein-coupled receptor

IEC:

Intestinal epithelial cell

IP3 :

Inositol 1,4,5-triphosphate

ITGA5:

Integrin alpha 5

LOX:

Lysyl oxidase

MAPK:

Mitogen-activated protein kinases

MMP:

Matrix metalloproteinase

MRP2:

Multidrug resistance-associated protein 2

MT:

Microtubule

NFκB:

Nuclear factor-kappa B

NSCLC:

Non-small cell lung carcinoma

PI3K:

Phosphoinositide 3-kinase

PKC:

Protein kinase C

PLC:

Phospholipase C

SNP:

Single nucleotide polymorphism

TGF-β:

Tumor growth factor beta

TME:

Tumor microenvironment

UTP:

Uridine 5′-triphosphate

VEGF:

Vascular epithelial growth factor

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Acknowledgements

F.P.G. is supported by a Canadian Institutes of Health Research operating grant (MOP-286567) and Natural Sciences and Engineering Research Council of Canada discovery grant (327128-2013). F.P.G. is a member of the FRQS-funded “Centre de Recherche du Centre hospitalier universitaire de Sherbrooke”.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

All procedures were performed according to the protocol # 328-13B that was approved by the Université de Sherbrooke Animal Care Committee and the Canadian Guidelines for Care and Use of Experimental Animals.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Faculté de Médecine et des Sciences de la Santé, Pavillon de Recherche Appliquée sur le Cancer, Université de Sherbrooke, Sherbrooke, QC, Canada

    Fernand-Pierre Gendron, Morgane Placet & Guillaume Arguin

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  1. Fernand-Pierre Gendron
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  2. Morgane Placet
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  3. Guillaume Arguin
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Correspondence to Fernand-Pierre Gendron .

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  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

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Gendron, FP., Placet, M., Arguin, G. (2017). P2Y2 Receptor Functions in Cancer: A Perspective in the Context of Colorectal Cancer. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 1051. Springer, Singapore. https://doi.org/10.1007/5584_2017_90

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