Tumor Suppression by Phospholipase C-beta3 via SHP-1-mediated Dephosphorylation of Stat5

Authors

Wenbin Xiao, La Jolla Institute for Allergy and Immunology, La Jolla, CA
Hong Hong, La Jolla Institute for Allergy and Immunology, La Jolla, CA
Yuko Kawakami, La Jolla Institute for Allergy and Immunology, La Jolla, CA
Yuko Kato, Chiba University, Chiba, Japan
Dianqing Wu, Yale University
Hiroki Yasudo, La Jolla Institute for Allergy and Immunology, La Jolla, CA
Akiko Kimura, National Institutes of Health
Hiromi Kubagawa, University of Alabama
Luigi F. Bertoli, Brookwood Medical Center, Birmingham, AL
Randall S. Davis, University of Alabama
Luan A. Chau, University of Western OntarioFollow
Joaquin Madrenas, University of Western OntarioFollow
Cyrus C. Hsia, University of Western OntarioFollow
Anargyros Xenocostas, University of Western OntarioFollow
Thomas J. Kipps, University of California, San Diego
Lothar Hennighausen, National Institutes of Health
Atsushi Iwama, Chiba University, Chiba, Japan
Hiromitsu Nakauchi, University of Tokyo
Toshiaki Kawakami, La Jolla Institute for Allergy and Immunology, La Jolla, CA

Document Type

Article

Publication Date

8-4-2009

Journal

Cancer Cell

Volume

16

Issue

2

First Page

161

Last Page

171

Abstract

Given its catalytic activity to generate diacylglycerol and inositol 1,4,5-trisphosphate, phospholipase C (PLC) is implicated in promoting cell growth. However, we found that PLC-beta3-deficient mice develop myeloproliferative disease, lymphoma, and other tumors. The mutant mice have increased numbers of hematopoietic stem cells with increased proliferative, survival, and myeloid-differentiative abilities. These properties are dependent on Stat5 and can be antagonized by the protein phosphatase SHP-1. Stat5-dependent cooperative transformation by active c-Myc and PLC-beta3 deficiency was suggested in mouse lymphomas in PLC-beta3(-/-) and in Emicro-myc;PLC-beta3(+/-) mice and human Burkitt's lymphoma cells. The same mechanism for malignant transformation seems to be operative in other human lymphoid and myeloid malignancies. Thus, PLC-beta3 is likely a tumor suppressor.

Notes

Published in: Cancer Cell, Volume 16, Issue 2, 161-171, 4 August 2009. doi: 10.1016/j.ccr.2009.05.018