Inhibiting G protein βγ signaling blocks prostate cancer progression and enhances the efficacy of paclitaxel

Prakash Paudyal; Qing Xie; Prasanna Kuma Vaddi; Michael D Henry; Songhai Chen

doi:10.18632/oncotarget.16428

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Inhibiting G protein βγ signaling blocks prostate cancer progression and enhances the efficacy of paclitaxel

Journal article

Open access

Peer reviewed

Inhibiting G protein βγ signaling blocks prostate cancer progression and enhances the efficacy of paclitaxel

Prakash Paudyal, Qing Xie, Prasanna Kuma Vaddi, Michael D Henry and Songhai Chen

Oncotarget, Vol.8(22), pp.36067-36081

05/30/2017

DOI: 10.18632/oncotarget.16428

PMCID: PMC5482639

PMID: 28415604

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Abstract

Aberrant activation of G protein-coupled receptors (GPCRs) is implicated in prostate cancer progression, but targeting them has been challenging because multiple GPCRs are involved in cancer progression. In this study, we tested the effect of blocking signaling via a hub through which multiple GPCRs converge - the G-protein Gβγ subunits. Inhibiting Gβγ signaling in several castration-resistant prostate cancer cell lines (i.e. PC3, DU145 and 22Rv1), impaired cell growth and migration in vitro, and halted tumor growth and metastasis in nude mice. The blockade of Gβγ signaling also diminished prostate cancer stem cell-like activities, by reducing tumorsphere formation in vitro and tumor formation in a limiting dilution assay in nude mice. Furthermore, Gβγ blockade enhanced the sensitivity of prostate cancer cells to paclitaxel treatment, both in vitro and in vivo. Together, our results identify a novel function of Gβγ in regulating prostate cancer stem-cell-like activities, and demonstrate that targeting Gβγ signaling is an effective approach in blocking prostate cancer progression and augmenting response to chemotherapy.

Prostatic Neoplasms - metabolism

GTP-Binding Protein gamma Subunits - metabolism

GTP-Binding Protein alpha Subunits - metabolism

Signal Transduction

Humans

Drug Resistance, Neoplasm

GTP-Binding Protein alpha Subunits - genetics

Male

Antineoplastic Agents - therapeutic use

Carcinogenesis

Paclitaxel - therapeutic use

Cell Growth Processes

Xenograft Model Antitumor Assays

Animals

Mice, Nude

Cell Line, Tumor

Mice

GTP-Binding Protein beta Subunits - metabolism

Neoplastic Stem Cells - physiology

Prostatic Neoplasms - drug therapy

Cell Movement

Details

Title: Subtitle: Inhibiting G protein βγ signaling blocks prostate cancer progression and enhances the efficacy of paclitaxel
Creators: Prakash Paudyal - The Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Qing Xie - The Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Prasanna Kuma Vaddi - The Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Michael D Henry - The Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Songhai Chen - The Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Oncotarget, Vol.8(22), pp.36067-36081
DOI: 10.18632/oncotarget.16428
PMID: 28415604
PMCID: PMC5482639
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: United States
Grant note: R01 GM094255 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 05/30/2017
Academic Unit: Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Urology; Internal Medicine
Record Identifier: 9984040383302771

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