Protein tyrosine phosphatase receptor type H (PTPRH)

Protein tyrosine phosphatase receptor type H (PTPRH) is a transmembrane protein and member of the protein tyrosine phosphatase family, characterized by extracellular fibronectin type III repeats, a single transmembrane domain, and a cytoplasmic catalytic domain[1][4]. It functions as a signaling regulator, influencing cellular processes such as growth, differentiation, apoptosis, and migration by dephosphorylating key proteins and modulating signal transduction pathways. PTPRH is overexpressed in several cancers, including colorectal, pancreatic, and non-small cell lung cancer, where it can promote tumorigenesis, cell proliferation, and glycolysis largely through the PI3K/AKT/mTOR pathway[5][6]. Loss-of-function mutations in PTPRH lead to heightened EGFR signaling, sensitizing tumors to EGFR inhibitors such as osimertinib[3]. PTPRH also contributes to contact inhibition and immune response modulation. Its status as a biomarker and therapeutic target is being investigated, particularly for patient stratification in cancers with aberrant EGFR activity[3][5][1][4].

Other names

SAP1R-PTP-HSAP-1Receptor-type tyrosine-protein phosphatase HStomach cancer-associated protein tyrosine phosphatase 1Transmembrane-type protein-tyrosine phosphatase type H

EGFR inhibitors (e.g., Osimertinib) can exploit dependence on EGFR signaling in PTPRH-mutant cancers[3]. Inhibition of PI3K/AKT/mTOR pathway can suppress PTPRH-driven tumor progression[5].