5'-nucleotidase domain-containing protein 2 (NT5DC2)

5'-Nucleotidase domain-containing protein 2 (NT5DC2) is an enzyme of the haloacid dehalogenase (HAD) superfamily that catalyzes hydrolysis of 5'-nucleotides, playing an important role in nucleotide metabolism[4][3]. It is highly expressed in a variety of cancers, including triple-negative breast cancer, hepatocellular carcinoma, and lung cancers, where it drives tumor cell proliferation, mediates immune suppression in the tumor microenvironment (notably through the MIF signaling axis), and promotes macrophage polarization towards the M2 phenotype[1][4]. NT5DC2 directly interacts with EGFR, stabilizing its expression by reducing EGFR ubiquitination, leading to enhanced tumor growth[2]. It is considered both a diagnostic and prognostic biomarker for several malignancies and represents an emerging therapeutic target, particularly because its knockdown inhibits cancer cell growth and induces apoptosis[1][2]. NT5DC2’s clinical manipulation carries risks due to its central metabolic and immunoregulatory functions[4][1].

Other names

5'-nucleotidase domain containing 2FLJ12442

Regulation of EGFR stability and signaling (promotes cell proliferation by stabilizing EGFR and reducing its ubiquitination); Modulation of immune signaling pathways (interacts with MIF, CD74, CXCR4, CD44 signaling, regulates macrophage function and immune cell infiltration); Nucleotide metabolism and enzymatic hydrolysis