BACKGROUND/ OBJECTIVES: Protein tyrosine phosphatase nonreceptor type 23 (PTPN23) has recently been associated with several human epithelial cancers via regulation of growth factor signaling. Colorectal carcinoma (CRC) is a leading cause for cancer-related death worldwide and is associated with aberrant epidermal (EGF) and vascular endothelial growth factor signaling. Here, we investigated whether PTPN23 might play a role in CRC. METHODS: Expression of PTPN23 was analyzed in CRC tissue by immunohistochemistry. PTPN23 was silenced in HT-29 cells to address the role of PTPN23 in EGF signaling, gene expression, and cell migration. RESULTS: PTPN23 silencing in HT-29 and Caco-2 intestinal epithelial cancer cells significantly enhanced activation of pro-oncogenic signaling molecules and genes promoting epithelial-to-mesenchymal transition (EMT) upon EGF treatment, while genes encoding tight junction proteins were significantly reduced. CONCLUSIONS: Our data clearly indicate that loss of PTPN23 is associated with increased activation of pro-oncogenic signaling pathways and an enhanced ability of human intestinal cancer cells to undergo EMT. Taken together, these findings show that PTPN23 acts as a tumor suppressor gene in CRC.
BACKGROUND/ OBJECTIVES: Protein tyrosine phosphatase nonreceptor type 23 (PTPN23) has recently been associated with several human epithelial cancers via regulation of growth factor signaling. Colorectal carcinoma (CRC) is a leading cause for cancer-related death worldwide and is associated with aberrant epidermal (EGF) and vascular endothelial growth factor signaling. Here, we investigated whether PTPN23 might play a role in CRC. METHODS: Expression of PTPN23 was analyzed in CRC tissue by immunohistochemistry. PTPN23 was silenced in HT-29 cells to address the role of PTPN23 in EGF signaling, gene expression, and cell migration. RESULTS: PTPN23 silencing in HT-29 and Caco-2 intestinal epithelial cancer cells significantly enhanced activation of pro-oncogenic signaling molecules and genes promoting epithelial-to-mesenchymal transition (EMT) upon EGF treatment, while genes encoding tight junction proteins were significantly reduced. CONCLUSIONS: Our data clearly indicate that loss of PTPN23 is associated with increased activation of pro-oncogenic signaling pathways and an enhanced ability of human intestinal cancer cells to undergo EMT. Taken together, these findings show that PTPN23 acts as a tumor suppressor gene in CRC.
Authors: Matthew A Odenwald; Wangsun Choi; Aaron Buckley; Nitesh Shashikanth; Nora E Joseph; Yitang Wang; Michael H Warren; Mary M Buschmann; Roman Pavlyuk; Jeffrey Hildebrand; Ben Margolis; Alan S Fanning; Jerrold R Turner Journal: J Cell Sci Date: 2016-10-21 Impact factor: 5.285