RUNX1T1 roles in neuroendocrine prostate cancer

Although indolent as prostate adenocarcinoma (PRAD) at first, the standard hormonal therapy inevitably induced metastatic and lethal neuroendocrine prostate cancer (NEPC) or small cell neuroendocrine prostate cancer (SCNPC), which currently has no specific and standard therapies due to a lack of understanding of the underlying biochemical mechanisms of progression.

In this study, we identified RUNX1 Partner Transcriptional Co-Repressor 1 (RUNX1T1) as a frequently amplified, AR-regulated gene in prostate cancer, with its high expression associated with NEPC progression. Our analysis of hallmarks and gene ontology based on RNA-seq of NEPC suggests that RUNX1T1 knockdown induced cell-cell adhesion and epithelial cell polarity, features related to a PRAD identity. Our functional analysis, based on gain- and loss-of-function in vitro/in vivo cell line models, revealed that RUNX1T1 is required for NEPC survival, stemness, and maintenance of SCNPC identity.