Protein tyrosine phosphatase type IVA member 3 (PTP4A3) (PTP4A3)

Protein tyrosine phosphatase type IVA member 3 (PTP4A3), also known as Phosphatase of Regenerating Liver 3 (PRL-3), is a key oncogenic phosphatase that promotes cancer cell proliferation, migration, and metastasis. It is a member of the PTP4A family of prenylated phosphatases and is localized to the plasma membrane and early endosomes, where it modulates signaling pathways such as PI3K/Akt, Src, and ERK (Wei et al., 2019, PMID: 31110038). PTP4A3 is frequently overexpressed in advanced stages of various malignancies, particularly in metastatic colorectal, gastric, and breast cancers, serving as a significant marker for poor clinical prognosis (Saha et al., 2001, PMID: 11546877). As a therapeutic target, PTP4A3 is approached through several modalities, including small molecule inhibitors like JMS-053, monoclonal antibodies such as PRL3-zumab, and RNA-targeting strategies. Targeting the PTP4A3 mRNA via siRNA or antisense oligonucleotides (ASOs) is a specific strategy aimed at preventing the translation of this pro-metastatic protein, thereby bypassing the structural challenges associated with the highly conserved phosphatase catalytic domain (Zeng et al., 2014, PMID: 24658274). While primarily intracellular, the occasional surface expression of PRL-3 in cancer cells has also allowed for the development of antibody-based therapies that trigger immune-mediated clearance of tumor cells (UniProt Q96PV6).

Other names

PRL-3PRL3Protein-tyrosine phosphatase of regenerating liver 3PTPCAAX3Protein tyrosine phosphatase 4A3

Inhibition of phosphatase catalytic activity, antibody-mediated cellular cytotoxicity (ADCC) against surface-expressed PRL-3, or RNA interference (RNAi) and antisense oligonucleotide (ASO) mediated degradation of PTP4A3 mRNA to reduce protein expression (Zeng et al., 2014, PMID: 24658274; Wei et al., 2019, PMID: 31110038).