ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
SRRM4 Expression and the Loss of REST Activity May Promote the Emergence of the Neuroendocrine Phenotype in Castration-Resistant Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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130 citing papers in PubMed, 178 citations in OpenAlex.
- Citron kinase activity controls alternative splicing events that drive prostate cancer growth.Science advances · 2026Article
- TMEM59L promotes neuroendocrine differentiation and enzalutamide resistance in prostate cancer by regulating MUC1/β-catenin/MYC axis.Clinical and translational medicine · 2026Article
- LRRC8D Suppresses Prostate Cancer Growth and Enhances Platinum Sensitivity via Modulation of CAV-1/STAT3 Signaling.Membranes · 2026Article
- USP2 is an androgen-repressed survival factor that stabilises oncoproteins to facilitate therapy resistance in prostate cancer.Cell death & disease · 2026Article
- Characterization and Evaluation of CD24 and NPY as Biomarkers for Metastatic Castration-Resistant Prostate Cancer.Diagnostics (Basel, Switzerland) · 2026Article
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Gene-body DNA methylation of ONECUT2 predicts its expression and prostate cancer aggressiveness in needle biopsies.Biomarker research · 2026Article
- The castration-resistant prostate cancer-associated SNP rs11067228 facilitates neuroendocrine differentiation through an enhancer-mediated chromatin interaction with SRRM4.International journal of biological sciences · 2026Article
- Mechanistic insights and molecular therapy for neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- Screening and validation of key genes involved in castration-resistant prostate cancer based on transcriptomics sequencing.Scientific reports · 2025Article
- Multi-omics analysis constructs a novel neuroendocrine prostate cancer classifier and classification system.Scientific reports · 2025Article
- The role of transcription factors in prostate cancer progression.Molecules and cells · 2025Review
- Defined cellular reprogramming of androgen receptor-active prostate cancer to neuroendocrine prostate cancer.bioRxiv : the preprint server for biology · 2025Article
- Machine learning-based identification of co-expressed genes in prostate cancer and CRPC and construction of prognostic models.Scientific reports · 2025Article
- PlexinD1 is a driver and a therapeutic target in advanced prostate cancer.EMBO molecular medicine · 2025Article
- LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer.Cell research · 2025Article
- Splice-switching antisense oligonucleotide controlling tumor suppressor REST is a novel therapeutic medicine for neuroendocrine cancer.Molecular therapy. Nucleic acids · 2024Article
- Understanding the function of Pax5 in development of docetaxel-resistant neuroendocrine-like prostate cancers.Cell death & disease · 2024Article
- Unveiling novel double-negative prostate cancer subtypes through single-cell RNA sequencing analysis.NPJ precision oncology · 2024Article
- SMARCA4 controls state plasticity in small cell lung cancer through regulation of neuroendocrine transcription factors and REST splicing.Journal of hematology & oncology · 2024Article
70 more citing papers are in PubMed but not listed here.
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18 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe neuroendocrine phenotype is associated with the development of metastatic castration-resistant prostate cancer (CRPC). Our objective was to characterize the molecular features of the neuroendocrine phenotype in CRPC. EXPERIMENTAL
designExpression of chromogranin A (CHGA), synaptophysin (SYP), androgen receptor (AR), and prostate-specific antigen (PSA) was analyzed by IHC in 155 CRPC metastases from 50 patients and in 24 LuCaP prostate cancer patient-derived xenografts (PDX). Seventy-one of 155 metastases and the 24 LuCaP xenograft lines were analyzed by whole-genome microarrays. REST splicing was verified by PCR.
resultsCoexpression of CHGA and SYP in >30% of cells was observed in 22 of 155 metastases (9 patients); 11 of the 22 metastases were AR(+)/PSA(+) (6 patients), 11/22 were AR-/PSA- (4 patients), and 4/24 LuCaP PDXs were AR(-)/PSA(-). By IHC, of the 71 metastases analyzed by whole-genome microarrays, 5 metastases were CHGA(+)/SYP(+)/AR(-), and 5 were CHGA(+)/SYP(+)/AR(+). Only CHGA(+)/SYP(+) metastases had a neuroendocrine transcript signature. The neuronal transcriptional regulator SRRM4 transcript was associated with the neuroendocrine signature in CHGA(+)/SYP(+) metastases and all CHGA(+)/SYP(+) LuCaP xenografts. In addition, expression of SRRM4 in LuCaP neuroendocrine xenografts correlated with a splice variant of REST that lacks the transcriptional repressor domain.
conclusions(i) Metastatic neuroendocrine status can be heterogeneous in the same patient, (ii) the CRPC neuroendocrine molecular phenotype can be defined by CHGA(+)/SYP(+) dual positivity, (iii) the neuroendocrine phenotype is not necessarily associated with the loss of AR activity, and (iv) the splicing of REST by SRRM4 could promote the neuroendocrine phenotype in CRPC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.