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Int. J. Mol. Sci. 2017, 18(11), 2494; doi:10.3390/ijms18112494

Proteinase-Activated Receptor 2 May Drive Cancer Progression by Facilitating TGF-β Signaling

1
First Department of Medicine, University Hospital Schleswig-Holstein, D-23538 Lübeck, Germany
2
Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, D-24105 Kiel, Germany
3
Department of General Pharmacology, Institute of Pharmacology, University Medicine Greifswald, D-17487 Greifswald, Germany
4
Department of General, Visceral and Vascular Surgery, Jena University Hospital, D-07747 Jena, Germany
*
Author to whom correspondence should be addressed.
Received: 6 November 2017 / Revised: 16 November 2017 / Accepted: 20 November 2017 / Published: 22 November 2017
(This article belongs to the Special Issue Cancer-Driver G Protein-Coupled Receptors as Therapeutic Targets)
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Abstract

The G protein-coupled receptor proteinase-activated receptor 2 (PAR2) has been implicated in various aspects of cellular physiology including inflammation, obesity and cancer. In cancer, it usually acts as a driver of cancer progression in various tumor types by promoting invasion and metastasis in response to activation by serine proteinases. Recently, we discovered another mode through which PAR2 may enhance tumorigenesis: crosstalk with transforming growth factor-β (TGF-β) signaling to promote TGF-β1-induced cell migration/invasion and invasion-associated gene expression in ductal pancreatic adenocarcinoma (PDAC) cells. In this chapter, we review what is known about the cellular TGF-β responses and signaling pathways affected by PAR2 expression, the signaling activities of PAR2 required for promoting TGF-β signaling, and the potential molecular mechanism(s) that underlie(s) the TGF-β signaling–promoting effect. Since PAR2 is activated through various serine proteinases and biased agonists, it may couple TGF-β signaling to a diverse range of other physiological processes that may or may not predispose cells to cancer development such as local inflammation, systemic coagulation and pathogen infection. View Full-Text
Keywords: pancreatic carcinoma; signaling; TGF-β; ALK5; PAR2; serine proteinases pancreatic carcinoma; signaling; TGF-β; ALK5; PAR2; serine proteinases
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Ungefroren, H.; Witte, D.; Rauch, B.H.; Settmacher, U.; Lehnert, H.; Gieseler, F.; Kaufmann, R. Proteinase-Activated Receptor 2 May Drive Cancer Progression by Facilitating TGF-β Signaling. Int. J. Mol. Sci. 2017, 18, 2494.

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