ArticleCancer research2021
RNA Splicing Factors SRRM3 and SRRM4 Distinguish Molecular Phenotypes of Castration-Resistant Neuroendocrine Prostate Cancer.
Article in Cancer research, 2021. 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, 51 citations in OpenAlex.
- Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- Characterization and Evaluation of CD24 and NPY as Biomarkers for Metastatic Castration-Resistant Prostate Cancer.Diagnostics (Basel, Switzerland) · 2026Article
- Patterns of intra- and intertumor phenotypic heterogeneity in lethal prostate cancer.The Journal of clinical investigation · 2025Article
- Article
- Impaired splicing machinery in craniopharyngiomas unveils PRPF8 and RAVER1 as novel biomarkers and therapeutic targets.Acta neuropathologica communications · 2025Article
- Framework for the Pathology Workup of Metastatic Castration-Resistant Prostate Cancer Biopsies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target.Molecular therapy. Oncology · 2024Article
- Insight into prostate cancer osteolytic metastasis by RelB coordination of IL-8 and S100A4.Clinical and translational medicine · 2024Article
- Splice-switching antisense oligonucleotide controlling tumor suppressor REST is a novel therapeutic medicine for neuroendocrine cancer.Molecular therapy. Nucleic acids · 2024Article
- SMARCA4 controls state plasticity in small cell lung cancer through regulation of neuroendocrine transcription factors and REST splicing.Journal of hematology & oncology · 2024Article
- Single-cell analysis of treatment-resistant prostate cancer: Implications of cell state changes for cell surface antigen-targeted therapies.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Characterization of zinc finger protein 536, a neuroendocrine regulator, using pan-cancer analysis.European journal of medical research · 2024Article
- Single Cell Analysis of Treatment-Resistant Prostate Cancer: Implications of Cell State Changes for Cell Surface Antigen Targeted Therapies.bioRxiv : the preprint server for biology · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Epigenetic regulation of mRNA mediates the phenotypic plasticity of cancer cells during metastasis and therapeutic resistance (Review).Oncology reports · 2024Review
- Targeting the fibroblast growth factor pathway in molecular subtypes of castration-resistant prostate cancer.The Prostate · 2024Article
- Comprehensively analysis of splicing factors to construct prognosis prediction classifier in prostate cancer.Journal of cellular and molecular medicine · 2023Article
- A novel GRK3-HDAC2 regulatory pathway is a key direct link between neuroendocrine differentiation and angiogenesis in prostate cancer progression.Cancer letters · 2023Article
- Minor intron splicing is critical for survival of lethal prostate cancer.Molecular cell · 2023Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
Neuroendocrine (NE) differentiation in metastatic castration-resistant prostate cancer (mCRPC) is an increasingly common clinical feature arising from cellular plasticity. We recently characterized two mCRPC phenotypes with NE features: androgen receptor (AR)-positive NE-positive amphicrine prostate cancer (AMPC) and AR-negative small cell or neuroendocrine prostate cancer (SCNPC). Here, we interrogated the regulation of RE1-silencing transcription factor (REST), a transcriptional repressor of neuronal genes, and elucidated molecular programs driving AMPC and SCNPC biology. Analysis of prostate cancer cell lines, mCRPC specimens, and LuCaP patient-derived xenograft models detected alternative splicing of REST to REST4 and attenuated REST repressor activity in AMPC and SCNPC. The REST locus was also hypermethylated and REST expression was reduced in SCNPC. While serine/arginine repetitive matrix protein 4 (SRRM4) was previously implicated in alternative splicing of REST in mCRPC, we detected SRRM3 expression in REST4-positive, SRRM4-negative AMPC, and SCNPC. In CRPC cell lines, SRRM3 induced alternative splicing of REST to REST4 and exacerbated the expression of REST-repressed genes. Furthermore, SRRM3 and SRRM4 expression defined molecular subsets of AMPC and SCNPC across species and tumor types. Two AMPC phenotypes and three SCNPC phenotypes were characterized, denoted either by REST attenuation and ASCL1 activity or by progressive activation of neuronal transcription factor programs, respectively. These results nominate SRRM3 as the principal REST splicing factor expressed in early NE differentiation and provide a framework to molecularly classify diverse NE phenotypes in mCRPC. SIGNIFICANCE: This study identifies SRRM3 as a key inducer of cellular plasticity in prostate cancer with neuroendocrine features and delineates distinct neuroendocrine phenotypes to inform therapeutic development and precision medicine applications.
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