Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway

Molecular Cancer

Research

Rafael Cubas¹  Qizhi Yao¹  Changyi Chen²  Sheng Zhang²  Min Li² 

[1] Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, TX, USA;Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, TX, USA;Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, TX, USA;

关键词: MAPK Pathway;    Panc02 Cell;    MEK1 Inhibitor PD98059;    Vector Control Group;    Hepatic Oval Cell;   

DOI  :  10.1186/1476-4598-9-253

 received in 2010-03-23, accepted in 2010-09-21,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundTrop2 is a cell-surface glycoprotein overexpressed by a variety of epithelial carcinomas with reported low to restricted expression in normal tissues. Expression of Trop2 has been associated with increased tumor aggressiveness, metastasis and decreased patient survival, but the signaling mechanisms mediated by Trop2 are still unknown. Here, we studied the effects murine Trop2 (mTrop2) exerted on tumor cellular functions and some of the signaling mechanisms activated by this oncogene.ResultsmTrop2 expression significantly increased tumor cell proliferation at low serum concentration, migration, foci formation and anchorage-independent growth. These in vitro characteristics translated to increased tumor growth in both subcutaneous and orthotopic pancreatic cancer murine models and also led to increased liver metastasis. mTrop2 expression also increased the levels of phosphorylated ERK1/2 mediating cell cycle progression by increasing the levels of cyclin D1 and cyclin E as well as downregulating p27. The activation of ERK was also observed in human pancreatic ductal epithelial cells and colorectal adenocarcinoma cells overexpressing human Trop2.ConclusionsThese findings demonstrate some of the pathogenic effects mediated by mTrop2 expression on cancer cells and the importance of targeting this cell surface glycoprotein. This study also provides the first indication of a molecular signaling pathway activated by Trop2 which has important implications for cancer cell growth and survival.

【 授权许可】

Unknown   
© Cubas et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.