ArticlePloS one2019
TCF4 induces enzalutamide resistance via neuroendocrine differentiation in prostate cancer.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- What genes are differentially expressed in individuals with schizophrenia? A systematic review.Molecular psychiatry · 2022Pooled it
- Multi-omics profiling of pancreatic neuroendocrine tumors: Interplay of genomic instability and the tumor microenvironment (Review).Oncology letters · 2026Review
- Study of ß-catenin signaling pathway modulated by PTHrP in cell and animal colorectal cancer models.Frontiers in oncology · 2026Article
- Prostate cancer cells converge to an inflammatory-like state upon metastatic dissemination.Nature communications · 2025Article
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Mechanisms and Therapeutic Strategies to Overcome Enzalutamide Resistance in Advanced Prostate Cancer.Serican journal of medicine · 2025Article
- Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment.Expert review of anticancer therapy · 2024Review
- An Atlas of Accessible Chromatin in Advanced Prostate Cancer Reveals the Epigenetic Evolution during Tumor Progression.Cancer research · 2024Article
- Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC.Nature communications · 2024Article
- Knockdown of EPS8 expression attenuates the proliferation of enzalutamide-resistant prostate cancer cells.American journal of cancer research · 2024Article
- Article
- Wnt Signaling and Therapeutic Resistance in Castration-Resistant Prostate Cancer.Current pharmacology reports · 2023Article
- Epiregulin expression and secretion is increased in castration-resistant prostate cancer.Frontiers in oncology · 2023Article
- Small interfering RNA targeting N-cadherin regulates cell proliferation and migration in enzalutamide-resistant prostate cancer.Oncology letters · 2022Article
- Exploring the Wnt Pathway as a Therapeutic Target for Prostate Cancer.Biomolecules · 2022Review
- Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation.Journal of experimental & clinical cancer research : CR · 2022Review
- miR-20a/TCF4 axis-mediated inhibition of hepatocytes proliferation impairs liver regeneration in mice PHx model by regulating CDC2 and CDC6.Journal of cellular and molecular medicine · 2021Article
- Transcription factor 4 expression in circulating tumor cells from castration-resistant prostate cancer.IJU case reports · 2021Article
- Novel Strategies for Treating Castration-Resistant Prostate Cancer.Biomedicines · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
In treating patients with castration resistant prostate cancer (CRPC), enzalutamide, the second-generation androgen receptor (AR) antagonist, is an accepted standard of care. However, clinical benefits are limited to a median time of 4.8 months because resistance inevitably emerges. To determine the mechanism of treatment resistance, we carried out a RNA sequence analysis and found increased expression levels of neuroendocrine markers in the enzalutamide-resistant LNCaP human prostate cancer (CaP) cell line when compared to the parental cell line. Subsequent studies demonstrated that Transcription Factor-4 (TCF4), a transcription factor implicated in WNT signaling, mediated neuroendocrine differentiation (NED) in response to enzalutamide treatment and was elevated in the enzalutamide-resistant LNCaP. In addition, we observed that PTHrP mediated enzalutamide resistance in tissue culture and inducible TCF4 overexpression resulted in enzalutamide-resistance in a mouse xenograft model. Finally, small molecule inhibitors of TCF4 or PTHrP partially reversed enzalutamide resistance in CaP cells. When tissues obtained from men who died of metastatic CaP were examined, a positive correlation was found between the expression levels of TCF4 and PTHrP. Taken together, the current results indicate that TCF4 induces enzalutamide resistance via NED in CaP.
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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.