ArticleOncotarget2017
Implications of PI3K/AKT inhibition on REST protein stability and neuroendocrine phenotype acquisition in prostate cancer cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 63 citations in OpenAlex.
- Proliferation of activated hepatic stellate cells requires REST.Molecular medicine (Cambridge, Mass.) · 2026Article
- Widespread activation and critical role of EMT and stemness in the neuroendocrine differentiation of prostate cancer (Review).Oncology reports · 2025Review
- The role of transcription factors in prostate cancer progression.Molecules and cells · 2025Review
- The role of neuroendocrine differentiation in treatment resistance of prostate cancer and intervention strategies.Frontiers in oncology · 2025Review
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- Functional Analysis of RE1 Silencing Transcription Factor as a Putative Tumor Suppressor in Human Endometrial Cancer.International journal of molecular sciences · 2024Article
- Targeting SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation of castration-resistant prostate cancer.Biology direct · 2024Article
- Regulation of Molecular Biomarkers Associated with the Progression of Prostate Cancer.International journal of molecular sciences · 2024Review
- Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023Review
- Review
- AR antagonists develop drug resistance through TOMM20 autophagic degradation-promoted transformation to neuroendocrine prostate cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Review
- Cholinergic regulation of vascular endothelial function by human ChATProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Identification of hub genes associated with head and neck squamous cell carcinoma by integrated bioinformatics approach and RNA-seq validation analysis.American journal of cancer research · 2023Article
- Molecular Imaging of Neuroendocrine Prostate Cancer by Targeting Delta-Like Ligand 3.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
- Novel biomarkers predict prognosis and drug-induced neuroendocrine differentiation in patients with prostate cancer.Frontiers in endocrinology · 2022Article
- Focus on the tumor microenvironment: A seedbed for neuroendocrine prostateFrontiers in cell and developmental biology · 2022Review
- An Insight on Novel Molecular Pathways in Metastatic Prostate Cancer: A Focus on DDR, MSI and AKT.International journal of molecular sciences · 2021Review
- Review
- RP11-462C24.1 suppresses proliferation and invasion of colorectal carcinoma cells by regulating HSP70 through PI3K/AKT signaling pathway.Human cell · 2021Article
Corrections and comments
- Erratum issuedCorrection: Implications of PI3K/AKT inhibition on REST protein stability and neuroendocrine phenotype acquisition in prostate cancer cells.2018 · Chen, Ruiqui [corrected to Chen, Ruiqi]
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells. The loss of REST by PI3K/AKT inhibition is through protein degradation mediated by the E3-ubiquitin ligase β-TRCP and REST phosphorylations at the S1024, S1027, and S1030 sites. Since AR inhibition can also deplete REST, the combinational inhibition of PI3K/AKT and AR further aggravated REST protein reduction. We profiled the transcriptomes of AKT and AR inhibitions in the LNCaP cells. The Gene Set Enrichment Analysis (GSEA) showed that these transcriptomes are highly correlated with the REST-regulated gene signature. Co-targeting AKT and AR resulted in a higher correlation comparing to those of single treatment. Comparing these transcriptomes to the t-NEPC gene signature in patients by GSEA, we observed that adding AKT inhibition to AR blockade enhanced the expression of neurogenesis-related genes and resulted in a stronger and broader upregulation of REST-regulated genes specific to t-NEPC. These results indicate that AKT pathway inhibition can induce neuroendocrine differentiation of PCa cells
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Registered trials
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.