ArticleCancers2021
LIMK2-NKX3.1 Engagement Promotes Castration-Resistant Prostate Cancer.
Article in Cancers, 2021. 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 15 papers, 1 of them a synthesis that pooled it.
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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Association Aamong Ppolymorphisms in the Aapoptosis-Rrelated NKX3-1, Caspase-3, Caspase-9, and BCL-2 Genes and Prostate Cancer Susceptibility From 9706 Cases and 12,567 Controls.Cancer reports (Hoboken, N.J.) · 2025Pooled it
- Novel therapeutic strategies for metastatic castration‑resistant prostate cancer: Beyond androgen receptor pathway inhibition (Review).International journal of oncology · 2026Review
- Correction: Sooreshjani et al. LIMK2-NKX3.1 Engagement Promotes Castration-Resistant Prostate Cancer.Cancers · 2026Article
- Genomic landscape and precision therapy in prostate cancer: current status and future directions.NPJ precision oncology · 2026Review
- Could GSTP1, PTEN and NKX3.1 gene expression be novel markers in the relationship between prostate cancer and epigenetics?BMC cancer · 2025Article
- LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1.Oncogene · 2025Article
- Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance.Frontiers in endocrinology · 2024Review
- Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review).International journal of oncology · 2023Review
- Review
- LIMK2: A Multifaceted kinase with pleiotropic roles in human physiology and pathologies.Cancer letters · 2023Review
- The identification of a two-gene prognostic model based on cisplatin resistance-related ceRNA network in small cell lung cancer.BMC medical genomics · 2023Article
- LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features.Cells · 2023Review
- Review
- LIMK2 Is a Novel Prognostic Biomarker and Correlates With Tumor Immune Cell Infiltration in Lung Squamous Cell Carcinoma.Frontiers in immunology · 2022Article
- Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models.Journal of biomedical science · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
NKX3.1's downregulation is strongly associated with prostate cancer (PCa) initiation, progression, and CRPC development. Nevertheless, a clear disagreement exists between NKX3.1 protein and mRNA levels in PCa tissues, indicating that its regulation at a post-translational level plays a vital role. This study identified a strong negative relationship between NKX3.1 and LIMK2, which is critical in CRPC pathogenesis. We identified that NKX3.1 degradation by direct phosphorylation by LIMK2 is crucial for promoting oncogenicity in CRPC cells and in vivo. LIMK2 also downregulates NKX3.1 mRNA levels. In return, NKX3.1 promotes LIMK2's ubiquitylation. Thus, the negative crosstalk between LIMK2-NKX3.1 regulates AR, ARv7, and AKT signaling, promoting aggressive phenotypes. We also provide a new link between NKX3.1 and PTEN, both of which are downregulated by LIMK2. PTEN loss is strongly linked with NKX3.1 downregulation. As NKX3.1 is a prostate-specific tumor suppressor, preserving its levels by LIMK2 inhibition provides a tremendous opportunity for developing targeted therapy in CRPC. Further, as NKX3.1 downregulates AR transcription and inhibits AKT signaling, restoring its levels by inhibiting LIMK2 is expected to be especially beneficial by co-targeting two driver pathways in tandem, a highly desirable requisite for developing effective PCa therapeutics.
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.