ArticleLaboratory investigation; a journal of technical methods and pathology2020
SOX2 has dual functions as a regulator in the progression of neuroendocrine prostate cancer.
Article in Laboratory investigation; a journal of technical methods and pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- pyVIPER: a fast and scalable Python package for protein activity estimation and master regulator analysis of single-cell RNA sequencing data.BMC bioinformatics · 2026Article
- c-Fos-driven metabolic switch of α-ketoglutarate orchestrates progression in prostate cancer.Cell death & disease · 2026Article
- Dynamic ecosystems of tumor drug resistance mechanisms: from molecular heterogeneity to systemic interventions.Apoptosis : an international journal on programmed cell death · 2026Review
- The role of SOX transcription factors in prostate cancer: Focusing on SOX2.Genes & diseases · 2025Review
- New frontiers in prostate cancer treatment from systemic therapy to targeted therapy.EMBO molecular medicine · 2025Review
- Widespread activation and critical role of EMT and stemness in the neuroendocrine differentiation of prostate cancer (Review).Oncology reports · 2025Review
- The molecular pathogenesis of SOX2 in prostate cancer.Discover oncology · 2025Review
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- Therapeutic Exploitation of Neuroendocrine Transdifferentiation Drivers in Prostate Cancer.Cells · 2024Review
- KIF1A promotes neuroendocrine differentiation in prostate cancer by regulating the OGT-mediated O-GlcNAcylation.Cell death & disease · 2024Article
- Neuroendocrine Prostate Cancer Drivers SOX2 and BRN2 Confer Differential Responses to Imipridones ONC201, ONC206, and ONC212 in Prostate Cancer Cell Lines.bioRxiv : the preprint server for biology · 2024Article
- Review
- Review
- Neuroendocrine prostate cancer drivers SOX2 and BRN2 confer differential responses to imipridones ONC201, ONC206, and ONC212 in prostate cancer cell lines.American journal of translational research · 2024Article
- Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023Review
- SOX2 expression in prostate cancer drives resistance to nuclear hormone receptor signaling inhibition through the WEE1/CDK1 signaling axis.Cancer letters · 2023Article
- Basal epithelial cells in prostate development, tumorigenesis, and cancer progression.Cell cycle (Georgetown, Tex.) · 2023Review
- Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer.Frontiers in cell and developmental biology · 2023Review
- Molecular mechanisms of neuroendocrine differentiation in prostate cancer progression.Journal of cancer research and clinical oncology · 2022Review
- Advances in neuroendocrine prostate cancer research: From model construction to molecular network analyses.Laboratory investigation; a journal of technical methods and pathology · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms underlying the lineage switching from prostate adenocarcinoma (AdPC) to lethal neuroendocrine prostate cancer (NEPC) have yet to be completely elucidated. In this study, RNA sequencing data from a unique patient-derived xenograft NEPC model and a clinical NEPC cohort were used to identify the potential genes driving NEPC progression. Enrichr analysis resulted in the identification of SRY-related HMG-box gene 2 (SOX2) as a potential repressor that causes decrease in the expression of AdPC specific genes in NEPC. Assays involving the stable overexpression of SOX2 in LNCaP and CWR22RV1 cells validated this role of SOX2 in vitro. Mechanistic studies showed that the repressor role of SOX2 was attributed to the marked global hypomethylation of histone H3, which was driven by the activation of lysine-specific demethylase 1 (LSD1). Furthermore, Enrichr also predicted SOX2 as a driver gene involved in the upregulation of NEPC specific genes. However, SOX2 alone could only marginally induce the expression of some neuroendocrine markers in vitro, which was consistent with previous reports. Moreover, we also elucidated the molecular features of LNCaP-SOX2 cells that may confer resistance to androgen-deprivation therapy (ADT) and the inclination toward neuroendocrine transdifferentiation. The results of this study reveal a novel mechanism for SOX2 in the progression of NEPC via LSD1-mediated global epigenetic modulation. This discovery suggests that LSD1 may be a selective target for the prevention of NEPC progression.
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