ArticleCell death & disease2017
AP4 modulated by the PI3K/AKT pathway promotes prostate cancer proliferation and metastasis of prostate cancer via upregulating L-plastin.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- An O-glycosylation-based prognostic signature for biochemical recurrence in prostate cancer identifiesTranslational andrology and urology · 2026Article
- Transcription factor activator protein 4 (AP4)-mediated intrinsic control of axon regeneration.Science advances · 2025Article
- LCP1 upregulation via EGFR signaling promotes oral cancer progression through the JAK2/STAT3/IL-1β axis.Cancer cell international · 2025Article
- TFAP4 Regulation of MCM5 Activates the PI3K/AKT Pathway to Promote Invasion and Metastasis of Gastric Cancer.Digestive diseases and sciences · 2025Article
- Genome-wide CRISPR screen identifies IRF1 and TFAP4 as transcriptional regulators of Galectin-9 in T cell acute lymphoblastic leukemia.Science advances · 2025Article
- LCP1 promotes ovarian cancer cell resistance to olaparib by activating the JAK2/STAT3 signalling pathway.Cancer biology & therapy · 2024Article
- circ_0006988 promotes gastric cancer cell proliferation, migration and invasion through miRNA-92a-2-5p/TFAP4 axis.Epigenomics · 2024Article
- Suppression of Tumor Cell Lactate-generating Signaling Pathways Eradicates Murine PTEN/p53-deficient Aggressive-variant Prostate Cancer via Macrophage Phagocytosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis.Cell death and differentiation · 2023Article
- Reversal of Lactate and PD-1-mediated Macrophage Immunosuppression Controls Growth of PTEN/p53-deficient Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies.Frontiers in molecular biosciences · 2023Article
- Consistent DNA Hypomethylations in Prostate Cancer.International journal of molecular sciences · 2022Article
- AP4 suppresses DNA damage, chromosomal instability and senescence via inducing MDC1/Mediator of DNA damage Checkpoint 1 and repressing MIR22HG/miR-22-3p.Molecular cancer · 2022Article
- Lymphocyte cytosolic protein 1 (L-plastin) I232F mutation impairs granulocytic proliferation and causes neutropenia.Blood advances · 2022Article
- Disulfiram-copper activates chloride currents and induces apoptosis with tyrosine kinase in prostate cancer cells.Asia-Pacific journal of clinical oncology · 2022Article
- L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis.Cell reports · 2022Article
- New Proteins Contributing to Immune Cell Infiltration and Pannus Formation of Synovial Membrane from Arthritis Diseases.International journal of molecular sciences · 2021Article
- Circular RNAs in prostate cancer: Biogenesis,biological functions, and clinical significance.Molecular therapy. Nucleic acids · 2021Review
- TFAP4 promotes the growth of prostate cancer cells by upregulating FOXK1.Experimental and therapeutic medicine · 2021Article
- LncRNA PAINT is associated with aggressive prostate cancer and dysregulation of cancer hallmark genes.International journal of cancer · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transition from androgen-dependent to metastatic castration-resistant prostate cancer (PCa) is a lethal event of uncertain molecular aetiology. Our previous studies demonstrated that L-plastin is involved in PCa invasion and metastasis and is upregulated by androgen and oestrogen in the hormone-dependent PCa cell line LNCaP. We recently found that L-plastin expression is consistently activated even after androgen deprivation, suggesting that androgen-independent transcription factors may regulate its expression. Herein, we performed sequential deletion and luciferase analysis of the L-plastin promoter and found that an androgen-independent regulatory factor prominently located in the region close to the transcription initiation site (-216 to +118) may facilitate L-plastin upregulation. AP4 was then identified as the relevant transcription activator that directly binds to the L-plastin promoter, as confirmed by EMSAs, supershift assays and CHIP-qPCR experiments. Moreover, we determined that the AP4/L-plastin axis is regulated by the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, contributing to PCa metastasis and castration resistance. Furthermore, we found that AP4 promotes PCa metastasis by upregulating L-plastin expression in vitro and in vivo. We collected a total of 136 PCa tissues and corresponding adjacent normal tissues from patients who underwent prostatectomy at Sun Yat-Sen Memorial Hospital from 2005 to 2015 and measured AP4 and L-plastin protein levels by immunohistochemistry. The results showed that AP4 levels strongly correlated with those of its downstream target gene L-plastin, were significantly upregulated in PCa tissues, were positively correlated with lymph node metastasis and Gleason scores over 7, and were an independent prognostic factor for patient survival. In summary, these findings support a plausible mechanism by which the AP4/L-plastin axis is regulated by the PI3K/AKT pathway in human PCa and may represent a novel therapeutic target in PCa treatment.
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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.