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GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling

Biomedical Sciences Graduate Program, School of Medicine, University of California, La Jolla, San Diego, CA 92093, USA
Department of Pharmacology, School of Medicine, University of California, La Jolla, San Diego, CA 92093, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work, and both are first co-authors.
Int. J. Mol. Sci. 2018, 19(7), 1886;
Received: 1 May 2018 / Revised: 20 June 2018 / Accepted: 21 June 2018 / Published: 27 June 2018
(This article belongs to the Special Issue Cancer-Driver G Protein-Coupled Receptors as Therapeutic Targets)
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G protein-coupled receptors (GPCRs) are a large diverse family of cell surface signaling receptors implicated in various types of cancers. Several studies indicate that GPCRs control many aspects of cancer progression including tumor growth, invasion, migration, survival and metastasis. While it is known that GPCR activity can be altered in cancer through aberrant overexpression, gain-of-function activating mutations, and increased production and secretion of agonists, the precise mechanisms of how GPCRs contribute to cancer progression remains elusive. Protease-activated receptors (PARs) are a unique class of GPCRs implicated in cancer. PARs are a subfamily of GPCRs comprised of four members that are irreversibly activated by proteolytic cleavage induced by various proteases generated in the tumor microenvironment. Given the unusual proteolytic irreversible activation of PARs, expression of receptors at the cell surface is a key feature that influences signaling responses and is exquisitely controlled by endocytic adaptor proteins. Here, we discuss new survey data from the Cancer Genome Atlas and the Genotype-Tissue Expression projects analysis of expression of all PAR family member expression in human tumor samples as well as the role and function of the endocytic sorting machinery that controls PAR expression and signaling of PARs in normal cells and in cancer. View Full-Text
Keywords: invasion; metastasis; breast cancer; arrestins; ARRDC3; lysosomes invasion; metastasis; breast cancer; arrestins; ARRDC3; lysosomes

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Arakaki, A.K.S.; Pan, W.-A.; Trejo, J. GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling. Int. J. Mol. Sci. 2018, 19, 1886.

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