alexa Atorvastatin prevents ATP-driven invasiveness via P2X7 and EHBP1 signaling in PTEN-expressing prostate cancer cells.
Immunology

Immunology

Journal of Clinical & Cellular Immunology

Author(s): Ghalali A, Wiklund F, Zheng H, Stenius U, Hgberg J

Abstract Share this page

Abstract Epidemiological studies indicate that statins, cholesterol-lowering drugs, prevent aggressive prostate cancer and other types of cancer. Employing essentially non-prostate cell lines, we previously showed that statins rapidly downregulate nuclear levels of phosphorylated Akt via P2X7, a purinergic receptor recently implicated in invasive growth. Here, we present studies on phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-positive prostatic cells. We document an involvement of EH domain-binding protein 1 (EHBP1), previously associated with aggressive prostate cancer and insulin-stimulated trafficking and cell migration, in P2X7 signaling. We also show that EHBP1 is essential for an anti-invasive effect of atorvastatin. Furthermore, EHBP1 interacted with P-Rex1, a guanine nucleotide exchange factor previously implicated in invasive growth. Mevalonate did not prevent this anti-invasive effect of atorvastatin. These data indicate that atorvastatin modulates invasiveness via P2X7, EHBP1 and P-Rex1. Interestingly, the interaction between EHBP1 and P-Rex1 was not induced by extracellular adenosine triphosphate (ATP), the endogenous P2X7 ligand, and statins counteracted invasiveness stimulated by extracellular ATP. In support of these experimental data, a population-based genetic analysis showed that a loss of function allele in the P2X7 gene (rs3751143) associated with non-aggressive cancer, and the common allele with aggressive cancer. Our data indicate a novel signaling pathway that inhibits invasiveness and that is druggable. Statins may reduce the risk of aggressive prostate cancer via P2X7 and by counteracting invasive effects of extracellular ATP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] This article was published in Carcinogenesis and referenced in Journal of Clinical & Cellular Immunology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

generalsci_healthcare[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords