Variations, and mutations have also been characterized in several PTP genes in human cancer in fact, now there are severalĮxamples of PTPs as tumor suppressors or the products of oncogenes ( Alonso et al. In contrast, the therapeutic potential of the PTPs has yet to be exploited fully. Understanding of the functions of PTKs in cancer has resulted in the development of novel therapeutics that target specificĬhanges in protein tyrosine phosphorylation-dependent signaling that drive cancer etiology ( Hunter 2009 Sliwkowski and Mellman 2013). Their functions disrupts the balance of reversible tyrosine phosphorylation, which impacts the normal patterns of intercellularĪnd intracellular signals and has been implicated in the etiology of various human diseases, including cancer. The dynamic regulation of phosphorylation of tyrosyl residues in proteins is maintained by the synchronized and complementaryĪctivity of two enzyme families: protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). The identification of FYN as a therapeutic target for breast tumors with heterozygous or homozygous loss of PTPN23. Overall, this mechanistic analysis of the tumor-suppressive function of PTPN23 in breast cancer supports Furthermore, double knockout of FYN and PTPN23 via CRISPR/CAS9 also attenuated tumor outgrowth from PTPN23 knockout Cal51 cells. Outgrowth from PTPN23-deficient BT474 cells was suppressed in a xenograft model in vivo upon treatment with AZD0530, an SFK We validated the underlying mechanism of PTPN23 function in breast tumorigenesisĪs that of a key phosphatase that normally suppresses the activity of FYN in two different models. (SFK) FYN as well as Tyr142 in β-catenin. In PTPN23-depleted tumors, we detected hyperphosphorylation of the autophosphorylation site tyrosine in the SRC family kinase Suppression of PTPN23 in Comma 1Dβ cells induced breast tumors within 56 wk. In an orthotopic transplantation mouse model. Therefore, we investigated the tumor-suppressive function of PTPN23 Now, our TCGA (The Cancer Genome Atlas) database analyses illustrate a correlation between low PTPN23 expressionĪnd poor survival in breast cancers of various subtypes. PTPome screen, our laboratory identified PTPN23 as a suppressor of cell motility and invasion in mammary epithelial and breastĬancer cells. Protein Tyrosine Phosphatase N23 ( PTPN23) resides in chromosomal region 3p21.3, which is hemizygously or homozygously lost in some breast cancer patients. Disruption of the balanced modulation of reversible tyrosine phosphorylation has been implicated in the etiology of various
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