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

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.

SUBMITTER: Bard-Chapeau EA

PROVIDER: S-EPMC3098128 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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

Bard-Chapeau Emilie A EA Li Shuangwei S Ding Jin J Zhang Sharon S SS Zhu Helen H HH Princen Frederic F Fang Diane D DD Han Tao T Bailly-Maitre Beatrice B Poli Valeria V Varki Nissi M NM Wang Hongyang H Feng Gen-Sheng GS

Cancer cell 20110501 5

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 diet ...[more]

PMID: 21575863

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