scholarly journals Protein tyrosine phosphatase receptor S acts as a metastatic suppressor in hepatocellular carcinoma by control of epithermal growth factor receptor-induced epithelial-mesenchymal transition

Hepatology ◽  
2015 ◽  
Vol 63 (1) ◽  
pp. 349-349
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Protein Tyrosine Phosphatase ◽  
Epithelial Mesenchymal Transition ◽  
Tyrosine Phosphatase ◽  
Growth Factor Receptor ◽  
Mesenchymal Transition ◽  
Protein Tyrosine

Molecular Mechanism and Prediction of Sorafenib Chemoresistance in Human Hepatocellular Carcinoma

2015 ◽  
Vol 33 (6) ◽  
pp. 771-779 ◽  
Author(s):  
Naoshi Nishida ◽  
Masayuki Kitano ◽  
Toshiharu Sakurai ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Kinase Inhibitor ◽  
Epithelial Mesenchymal Transition ◽  
Growth Factor Receptor ◽  
Stem Cell Markers ◽  
Mesenchymal Transition ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Underlying Mechanisms

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide, and prognosis remains unsatisfactory when the disease is diagnosed at an advanced stage. Many molecular targeted agents are being developed for the treatment of advanced HCC; however, the only promising drug to have been developed is sorafenib, which acts as a multi-kinase inhibitor. Unfortunately, a subgroup of HCC is resistant to sorafenib, and the majority of these HCC patients show disease progression even after an initial satisfactory response. To date, a number of studies have examined the underlying mechanisms involved in the response to sorafenib, and trials have been performed to overcome the acquisition of drug resistance. The anti-tumor activity of sorafenib is largely attributed to the blockade of the signals from growth factors, such as vascular endothelial growth factor receptor and platelet-derived growth factor receptor, and the downstream RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade. The activation of an escape pathway from RAF/MEK/ERK possibly results in chemoresistance. In addition, there are several features of HCCs indicating sorafenib resistance, such as epithelial-mesenchymal transition and positive stem cell markers. Here, we review the recent reports and focus on the mechanism and prediction of chemoresistance to sorafenib in HCC.

scholarly journals The protein tyrosine phosphatase Pez regulates TGFβ, epithelial–mesenchymal transition, and organ development

2007 ◽  
Vol 178 (7) ◽  
pp. 1223-1235 ◽  
Author(s):  
Leila Wyatt ◽  
Carol Wadham ◽  
Lesley A. Crocker ◽  
Michael Lardelli ◽  
Yeesim Khew-Goodall
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Crucial Role ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mdck Cells ◽  
Tyrosine Phosphatase ◽  
Pharyngeal Arches ◽  
Mesenchymal Transition ◽  
Protein Tyrosine ◽  
And Function

Epithelial–mesenchymal transition (EMT), crucial during embryogenesis for new tissue and organ formation, is also considered to be a prerequisite to cancer metastasis. We report here that the protein tyrosine phosphatase Pez is expressed transiently in discrete locations in developing brain, heart, pharyngeal arches, and somites in zebrafish embryos. We also find that Pez knock-down results in defects in these organs, indicating a crucial role in organogenesis. Overexpression of Pez in epithelial MDCK cells causes EMT, with a drastic change in cell morphology and function that is accompanied by changes in gene expression typical of EMT. Transfection of Pez induced TGFβ signaling, critical in developmental EMT with a likely role also in oncogenic EMT. In zebrafish, TGFβ3 is co- expressed with Pez in a number of tissues and its expression was lost from these tissues when Pez expression was knocked down. Together, our data suggest Pez plays a crucial role in organogenesis by inducing TGFβ and EMT.

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