Regulator of G Protein Signaling 17 as a Negative Modulator of GPCR Signaling in Multiple Human Cancers

Michael P Hayes; David L Roman

doi:10.1208/s12248-016-9894-1

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Regulator of G Protein Signaling 17 as a Negative Modulator of GPCR Signaling in Multiple Human Cancers

Journal article

Open access

Peer reviewed

Regulator of G Protein Signaling 17 as a Negative Modulator of GPCR Signaling in Multiple Human Cancers

Michael P Hayes and David L Roman

The AAPS journal, Vol.18(3), pp.550-559

05/2016

DOI: 10.1208/s12248-016-9894-1

PMCID: PMC5256612

PMID: 26928451

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Abstract

Regulators of G protein signaling (RGS) proteins modulate G protein-coupled receptor (GPCR) signaling networks by terminating signals produced by active Gα subunits. RGS17, a member of the RZ subfamily of RGS proteins, is typically only expressed in appreciable amounts in the human central nervous system, but previous works have shown that RGS17 expression is selectively upregulated in a number of malignancies, including lung, breast, prostate, and hepatocellular carcinoma. In addition, this upregulation of RGS17 is associated with a more aggressive cancer phenotype, as increased proliferation, migration, and invasion are observed. Conversely, decreased RGS17 expression diminishes the response of ovarian cancer cells to agents commonly used during chemotherapy. These somewhat contradictory roles of RGS17 in cancer highlight the need for selective, high-affinity inhibitors of RGS17 to use as chemical probes to further the understanding of RGS17 biology. Based on current evidence, these compounds could potentially have clinical utility as novel chemotherapeutics in the treatment of lung, prostate, breast, and liver cancers. Recent advances in screening technologies to identify potential inhibitors coupled with increasing knowledge of the structural requirements of RGS-Gα protein-protein interaction inhibitors make the future of drug discovery efforts targeting RGS17 promising. This review highlights recent findings related to RGS17 as both a canonical and atypical RGS protein, its role in various human disease states, and offers insights on small molecule inhibition of RGS17.

Neoplasms - metabolism

Protein Structure, Secondary

Humans

Drug Discovery - trends

RGS Proteins - physiology

Antineoplastic Agents - administration & dosage

Antineoplastic Agents - chemistry

Neoplasms - drug therapy

Antineoplastic Agents - metabolism

Animals

Signal Transduction - drug effects

RGS Proteins - chemistry

Signal Transduction - physiology

RGS Proteins - antagonists & inhibitors

Receptors, G-Protein-Coupled - chemistry

Receptors, G-Protein-Coupled - physiology

Details

Title: Subtitle: Regulator of G Protein Signaling 17 as a Negative Modulator of GPCR Signaling in Multiple Human Cancers
Creators: Michael P Hayes - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, Iowa, USA
David L Roman - , 115 S. Grand Avenue, S327 PHAR, Iowa City, Iowa, 52242, USA. david-roman@uiowa.edu
Resource Type: Journal article
Publication Details: The AAPS journal, Vol.18(3), pp.550-559
Publisher: United States
DOI: 10.1208/s12248-016-9894-1
PMID: 26928451
PMCID: PMC5256612
ISSN: 1550-7416
eISSN: 1550-7416
Grant note: R01 CA160470 / NCI NIH HHS T32 GM067795 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 05/2016
Academic Unit: Pharmacy; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
Record Identifier: 9984065485202771

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