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Cancer Cell. 2011 May 17;19(5):629-39. doi: 10.1016/j.ccr.2011.03.023.

Ptpn11/Shp2 acts as a tumor suppressor in hepatocellular carcinogenesis.

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  • 1Department of Pathology, University of California San Diego, La Jolla, CA 92093-0864, USA.

Abstract

The human gene Ptpn11, which encodes the tyrosine phosphatase Shp2, may act as a proto-oncogene because dominantly activating mutations have been detected in several types of leukemia. Herein we report a tumor-suppressor function of Shp2. Hepatocyte-specific deletion of Shp2 promotes inflammatory signaling through the Stat3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and development of tumors in aged mice. Furthermore, Shp2 ablation dramatically enhanced diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) development, which was abolished by concurrent deletion of Shp2 and Stat3 in hepatocytes. Decreased Shp2 expression was detected in a subfraction of human HCC specimens. Thus, in contrast to the leukemogenic effect of dominant-active mutants, Ptpn11/Shp2 has a tumor-suppressor function in liver.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21575863
[PubMed - indexed for MEDLINE]
PMCID:
PMC3098128
Free PMC Article

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