One cut domain family member 2 (ONECUT2)

One cut domain family member 2 (ONECUT2) is a transcription factor characterized by a CUT domain and a homeodomain, which cooperate to bind DNA and regulate gene expression[2][4]. ONECUT2 is mainly expressed in tissues such as the liver, gallbladder, small intestine, and duodenum, as well as the nervous system[1][3][6]. It controls programs involved in cell proliferation, adhesion, migration, differentiation, metabolism, and epigenomic remodeling, often via modulation of PRC2-complex-mediated histone methylation[1][7]. ONECUT2 is a context-dependent oncogenic driver implicated in tumor progression, lineage plasticity, and drug resistance, with a specific role in neuroendocrine and metastatic castration-resistant prostate cancer, as well as lung adenocarcinoma[1][3][5][7]. Experimental small molecule inhibitors against ONECUT2 are being explored as therapeutic agents in cancer[7]. Elevated expression of ONECUT2 may serve as a biomarker for aggressive disease phenotypes and tumor cell plasticity[7]. Targeting ONECUT2 requires caution due to its broad biological functions and tissue distribution[3][6].

Other names

ONECUT2One cut domain family member 2OC-2HNF-6-betaHepatocyte nuclear factor 6-betaONECUT-2One cut homeobox 2Transcription factor ONECUT-2HNF6Bonecut 2OC2

Direct inhibition of transcriptional activity (by small molecule inhibitors); Epigenetic modulation via inhibiting histone methyltransferase EZH2, thus impacting genes regulated by ONECUT2