Disabled homolog 2 (DAB2) (DAB2)

Disabled homolog 2 (DAB2), also historically referred to as Stagnin, is a multifunctional adaptor protein that serves as a critical tumor suppressor in several human cancers [5, 8]. It was originally named 'Stagnin' because its expression is specifically induced during the growth stagnation phase of cell culture, indicating its involvement in growth arrest and the maintenance of cell cycle control [8, 12]. Biologically, DAB2 is a key component of the endocytic machinery, facilitating clathrin-mediated endocytosis of various receptors and signaling molecules, and it acts as a negative regulator of the Wnt/beta-catenin pathway while promoting TGF-beta signaling [5, 20]. In many malignancies, including ovarian, breast, and prostate cancer, DAB2 expression is frequently downregulated or lost, often as a result of epigenetic silencing through promoter hypermethylation [15]. This loss is strongly associated with increased tumor aggressiveness, epithelial-to-mesenchymal transition (EMT), and poor clinical outcomes [6, 17]. While there are currently no approved drugs that directly target DAB2, it remains a significant biomarker for cancer prognosis and a focal point for research into therapeutic restoration and gene delivery strategies [6, 10].

Other names

StagninDOC-2Differentially expressed in ovarian cancer 2Disabled-2p96

No specific direct-acting small-molecule drugs are currently approved; therapeutic strategies focus on the restoration of its tumor-suppressive expression through epigenetic modulation (e.g., DNA methyltransferase inhibitors) or gene therapy.