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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Overexpression of protein phosphatase non-receptor type 11 (PTPN11) in gastric carcinomas
Jin Soo Kim1, Ok Ran Shin, Hyung Keun Kim
1Department of Internal Medicine, College of Medicine, Uijongbu St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Background:
Tyrosine phosphorylation and dephosphorylation by protein tyrosine kinases and phosphatases (PTPs), respectively, play crucial roles in cellular signal transduction. Protein phosphatase non-receptor type 11 (PTPN11) is a positive signaling PTP that activates RAS and ERK signaling. Also, the PTPN11 binds with CagA of Helicobacter pylori in gastric epithelial cells.
Aim:
The aim of this study was to explore whether alteration of PTPN11 protein expression is a feature of gastric cancer cells.
Methods:
We analyzed PTPN11 expression in 92 gastric cancer tissues by immunohistochemistry using a tissue microarray method.
Results:
The gastric cancers expressed PTPN11 in 78 (87%) specimens, while the epithelial cells in normal gastric mucosa did not display any PTPN11 immunoreactivity. The PTPN11 expression in the cancers was associated with the tubular morphology (versus signet ring cell type), the Lauren's intestinal type (versus diffuse type), and the advanced gastric cancer type (versus early gastric cancer type).
Conclusion:
Our data indicate that gastric cancers display a higher expression of PTPN11 protein than the normal cells, suggesting that neo-expression of this positive signaling protein in the cells might play a role in the cancer development. Also, the higher expression of PTPN11 in tubular and intestinal types, where Helicobacter pylori has a definite role in the development of the cancers, suggest a possibility that PTPN11 might play a role in regulation in Helicobacter pylori pathogenesis the gastric cancers.
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