ArticleThe Journal of clinical investigation2021
MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- lncAPNet enables the deciphering of lncRNA-mRNA connections in patient transcriptomic data.Bioinformatics advances · 2026Article
- FAM111B promotes prostate cancer progression by inhibiting apoptosis via ATF3 suppression and MAPK pathway activation: a novel biomarker and therapeutic target.Cancer cell international · 2025Article
- p53 transcriptionally activates DCP1B to suppress tumor progression and enhance tumor sensitivity to PI3K blockade in non-small cell lung cancer.Cell death and differentiation · 2025Article
- Polystyrene microspheres could inhibit the ferroptosis of prostate cancer cells via USP39/IGF2BP3/MAPK4 axis.Journal of translational medicine · 2025Article
- A Spermidine Derivative Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting the MAPK4/AKT Signaling Pathway.Foods (Basel, Switzerland) · 2025Article
- Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review).Oncology letters · 2025Review
- C6 and KLRG2 are pyroptosis subtype-related prognostic biomarkers and correlated with tumor-infiltrating lymphocytes in lung adenocarcinoma.Scientific reports · 2024Article
- Article
- GATA2 promotes castration-resistant prostate cancer development by suppressing IFN-β axis-mediated antitumor immunity.Oncogene · 2024Article
- Network pharmacology and experimental validation to explore the role and potential mechanism of Liuwei Dihuang Decoction in prostate cancer.BMC complementary medicine and therapies · 2024Article
- MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer.Cancer innovation · 2024Article
- Article
- Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance.Frontiers in endocrinology · 2024Review
- Molecular Insight into Prostate Cancer: Preventive Role of Selective Bioactive Molecules.Life (Basel, Switzerland) · 2023Review
- Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy.PLoS biology · 2023Article
- DeeP4med: deep learning for P4 medicine to predict normal and cancer transcriptome in multiple human tissues.BMC bioinformatics · 2023Article
- MAPK4 predicts poor prognosis and facilitates the proliferation and migration of glioma through the AKT/mTOR pathway.Cancer medicine · 2023Article
- Addressing the Reciprocal Crosstalk between the AR and the PI3K/AKT/mTOR Signaling Pathways for Prostate Cancer Treatment.International journal of molecular sciences · 2023Review
- Identification of a novel senescence-associated signature to predict biochemical recurrence and immune microenvironment for prostate cancer.Frontiers in immunology · 2023Article
- Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostate cancer (PCa) is the second leading cause of cancer death in American men. Androgen receptor (AR) signaling is essential for PCa cell growth/survival and remains a key therapeutic target for lethal castration-resistant PCa (CRPC). GATA2 is a pioneer transcription factor crucial for inducing AR expression/activation. We recently reported that MAPK4, an atypical MAPK, promotes tumor progression via noncanonical activation of AKT. Here, we demonstrated that MAPK4 activated AR by enhancing GATA2 transcriptional expression and stabilizing GATA2 protein through repression of GATA2 ubiquitination/degradation. MAPK4 expression correlated with AR activation in human CRPC. Concerted activation of both GATA2/AR and AKT by MAPK4 promoted PCa cell proliferation, anchorage-independent growth, xenograft growth, and castration resistance. Conversely, knockdown of MAPK4 decreased activation of both AR and AKT and inhibited PCa cell and xenograft growth, including castration-resistant growth. Both GATA2/AR and AKT activation were necessary for MAPK4 tumor-promoting activity. Interestingly, combined overexpression of GATA2 plus a constitutively activated AKT was sufficient to drive PCa growth and castration resistance, shedding light on an alternative, MAPK4-independent tumor-promoting pathway in human PCa. We concluded that MAPK4 promotes PCa growth and castration resistance by cooperating parallel pathways of activating GATA2/AR and AKT and that MAPK4 is a novel therapeutic target in PCa, especially CRPC.
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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.