A Critical Role of Gβγ in Tumorigenesis and Metastasis of Breast Cancer

Xiaoyun Tang; Zhizeng Sun; Caitlin Runne; Joshua Madsen; Frederick Domann; Michael Henry; Fang Lin; Songhai Chen

doi:10.1074/jbc.M110.206615

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A Critical Role of Gβγ in Tumorigenesis and Metastasis of Breast Cancer

Journal article

Open access

Peer reviewed

A Critical Role of Gβγ in Tumorigenesis and Metastasis of Breast Cancer

Xiaoyun Tang, Zhizeng Sun, Caitlin Runne, Joshua Madsen, Frederick Domann, Michael Henry, Fang Lin and Songhai Chen

The Journal of biological chemistry, Vol.286(15), pp.13244-13254

04/15/2011

DOI: 10.1074/jbc.M110.206615

PMCID: PMC3075671

PMID: 21349837

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Abstract

A growing body of evidence indicates that G protein-coupled receptors (GPCRs) are involved in breast tumor progression and that targeting GPCRs may be a novel adjuvant strategy in cancer treatment. However, due to the redundant role of multiple GPCRs in tumor development, it may be necessary to target a common signaling component downstream of these receptors to achieve maximum efficacy. GPCRs transmit signals through heterotrimeric G proteins composed of Gα and Gβγ subunits. Here we evaluated the role of Gβγ in breast tumor growth and metastasis both in vitro and in vivo . Our data show that blocking Gβγ signaling with Gα t or small molecule inhibitors blocked serum-induced breast tumor cell proliferation as well as tumor cell migration induced by various GPCRs in vitro . Moreover, induced expression of Gα t in MDA-MB-231 cells inhibited primary tumor formation and retarded growth of existing breast tumors in nude mice. Blocking Gβγ signaling also dramatically reduced the incidence of spontaneous lung metastasis from primary tumors and decreased tumor formation in the experimental lung metastasis model. Additional studies indicate that Gβγ signaling may also play a role in the generation of a tumor microenvironment permissive for tumor progression, because the inhibition of Gβγ signaling attenuated leukocyte infiltration and angiogenesis in primary breast tumors. Taken together, our data demonstrate a critical role of Gβγ signaling in promoting breast tumor growth and metastasis and suggest that targeting Gβγ may represent a novel therapeutic approach for breast cancer.

Molecular Bases of Disease

G Protein-coupled Receptors (GPCR)

Mouse

Signal Transduction

G Proteins

Tumor Growth

Breast Cancer

Tumor Metastasis

Details

Title: Subtitle: A Critical Role of Gβγ in Tumorigenesis and Metastasis of Breast Cancer
Creators: Xiaoyun Tang - From the Departments of
Zhizeng Sun - From the Departments of
Caitlin Runne - From the Departments of
Joshua Madsen - Radiation Oncology
Frederick Domann - Radiation Oncology
Michael Henry - Molecular Physiology and Biophysics
Fang Lin - Anatomy and Cell Biology, and
Songhai Chen - From the Departments of
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.286(15), pp.13244-13254
DOI: 10.1074/jbc.M110.206615
PMID: 21349837
PMCID: PMC3075671
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: R01CA115438 / National Institutes of Health
Alternative title: Gβγ and Breast Tumor Growth and Metastasis
Language: English
Date published: 04/15/2011
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Pathology; Iowa Neuroscience Institute; Surgery; Radiation Oncology; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Urology; Internal Medicine
Record Identifier: 9984025696802771

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