ArticleOncogene2025
A TBX2-driven signaling switch from androgen receptor to glucocorticoid receptor confers therapeutic resistance in prostate cancer.
Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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
6 citing papers in PubMed.
- A TBX2-HLX Regulatory Axis Is Associated with Advanced Prostate Cancer.Biomedicines · 2026Article
- Article
- Comparative analysis for optimal LSD1 inhibitors evaluation techniques: pros and cons.Journal of pharmaceutical analysis · 2026Review
- Targeting FANCD2 to overcome enzalutamide resistance in prostate cancer.Cancer & metabolism · 2026Article
- Identification of epigenetic monotherapy candidates in taxane-resistant CRPC.Turkish journal of biology = Turk biyoloji dergisi · 2025Article
- Editorial: Molecular drivers of prostate cancer pathogenesis and therapy resistance.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Recent studies suggest that glucocorticoid receptor (GR) activation can cause enzalutamide resistance in advanced prostate cancer (PCa) via functional bypass of androgen receptor (AR) signaling. However, the specific molecular mechanism(s) driving this process remain unknown. We have previously reported that the transcription factor TBX2 is over-expressed in castrate-resistant prostate cancer (CRPC). In this study, using human PCa and CRPC cell line models, we demonstrate that TBX2 downregulates AR and upregulates GR through direct transcriptional regulation. TBX2 also activated the GR via TBX2-GR protein-protein interactions. Together, TBX2-driven repression of AR and activation of GR resulted in enzalutamide resistance. Our laboratory findings are supported by clinical samples, which show a similar and consistent pattern of transcriptional activity among TBX2, AR and GR across patient cohorts. Notably, we report that SP2509, an allosteric inhibitor of the demethylase-independent function of LSD1 (a TBX2-interacting protein in the COREST complex) disrupts both TBX2-LSD1 and TBX2-GR protein-protein interactions, revealing a unique mode of SP2509 action in CRPC. Taken together, our study identifies the TBX2-driven AR- to GR- signaling switch as a molecular mechanism underlying enzalutamide resistance and provides key insights into a potential therapeutic approach for targeting this switch by disrupting TBX2-GR and TBX2-LSD1 protein-protein interactions.
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.