ArticleOncogene2018
Orphan nuclear receptor TLX contributes to androgen insensitivity in castration-resistant prostate cancer via its repression of androgen receptor transcription.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed, 30 citations in OpenAlex.
- Nuclear receptor TLX functions to promote cancer stemness and EMT in prostate cancer via its direct transactivation of CD44 and stem cell-regulatory transcription factors.British journal of cancer · 2024Article
- DNA damage-mediated FTO downregulation promotes CRPC progression by inhibiting FOXO3a via an miScience · 2024Article
- Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance.Frontiers in endocrinology · 2024Review
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review).International journal of oncology · 2023Review
- The nuclear receptor TLX (NR2E1) inhibits growth and progression of triple- negative breast cancer.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Interaction between prostate cancer stem cells and bone microenvironment regulates prostate cancer bone metastasis and treatment resistance.Journal of Cancer · 2022Review
- TLX, an Orphan Nuclear Receptor With Emerging Roles in Physiology and Disease.Endocrinology · 2021Review
- Glial PAMPering and DAMPening of Adult Hippocampal Neurogenesis.Brain sciences · 2021Review
- Orphan nuclear receptors as regulators of intratumoral androgen biosynthesis in castration-resistant prostate cancer.Oncogene · 2021Review
- Orphan nuclear receptor TLX promotes immunosuppression via its transcriptional activation of PD-L1 in glioma.Journal for immunotherapy of cancer · 2021Article
- Identification of NNeurosurgical review · 2021Article
- The role of N-cadherin/c-Jun/NDRG1 axis in the progression of prostate cancer.International journal of biological sciences · 2021Article
- Emerging role of tumor cell plasticity in modifying therapeutic response.Signal transduction and targeted therapy · 2020Review
- Towards understanding androgen receptor-independent prostate cancer: an evolving paradigm.Translational cancer research · 2020Article
- MLL5α activates AR/NDRG1 signaling to suppress prostate cancer progression.American journal of cancer research · 2020Article
- Targeting GRP78-dependent AR-V7 protein degradation overcomes castration-resistance in prostate cancer therapy.Theranostics · 2020Article
- Tumorigenic effects of TLX overexpression in HEK 293T cells.Cancer reports (Hoboken, N.J.) · 2019Article
- Article
- Computer-Aided Discovery of Small Molecule Inhibitors of Transcriptional Activity of TLX (NR2E1) Nuclear Receptor.Molecules (Basel, Switzerland) · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The metastatic castration-resistant prostate cancer (CRPC) is a lethal form of prostate cancer, in which the expression of androgen receptor (AR) is highly heterogeneous. Indeed, lower AR expression and attenuated AR signature activity is shown in CRPC tissues, especially in the subset of neuroendocrine prostate cancer (NEPC) and prostate cancer stem-like cells (PCSCs). However, the significance of AR downregulation in androgen insensitivity and de-differentiation of tumor cells in CRPC is poorly understood and much neglected. Our previous study shows that the orphan nuclear receptor TLX (NR2E1), which is upregulated in prostate cancer, plays an oncogenic role in prostate carcinogenesis by suppressing oncogene-induced senescence. In the present study, we further established that TLX exhibited an increased expression in metastatic CRPC. Further analyses showed that overexpression of TLX could confer resistance to androgen deprivation and anti-androgen in androgen-dependent prostate cancer cells in vitro and in vivo, whereas knockdown of endogenous TLX could potentiate the sensitivity to androgen deprivation and anti-androgen in prostate cancer cells. Our study revealed that the TLX-induced resistance to androgen deprivation and anti-androgen was mediated through its direct suppression of AR gene transcription and signaling in both androgen-stimulated and -unstimulated prostate cancer cells. We also characterized that TLX could bind directly to AR promoter and repress AR transcription by recruitment of histone modifiers, including HDAC1, HDAC3, and LSD1. Together, our present study shows, for the first time, that TLX can contribute to androgen insensitivity in CRPC via repression of AR gene transcription and signaling, and also implicates that targeting the druggable TLX may have a potential therapeutic significance in CRPC management, particularly in NEPC and PCSCs.
Indexed as
Identifiers
What OpenQuestion holds
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.