ArticleInternational journal of cancer2020
The functional interlink between AR and MMP9/VEGF signaling axis is mediated through PIP5K1α/pAKT in prostate cancer.
Article in International journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review.International journal of molecular sciences · 2021Pooled it
- Role of Androgen Receptor in Melanoma: Mechanisms of Tumor Progression, Immune Evasion, and Therapeutic Implications.Cancers · 2025Review
- Biochemical Study of Bilberry Extract Potential in Preventing Retinal Damage in Rat Model of Diabetes Induced by Streptozotocin/Nicotinamide.Life (Basel, Switzerland) · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.Molecular cancer · 2024Review
- Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery.Biomedicines · 2023Review
- The Potential of Glycyrrhiza from "Medicine Food Homology" in the Fight against Digestive System Tumors.Molecules (Basel, Switzerland) · 2023Review
- [Cyclin A1 affects the invasion, metastasis, and prognosis of hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Screening of key genes in childhood asthma based on bioinformatics analysis.Translational pediatrics · 2023Article
- Fibrotic remodeling and tissue regeneration mechanisms define the therapeutic potential of human muscular progenitors.Bioengineering & translational medicine · 2023Article
- Lactoferrin and Activated Protein C: Potential Role in Prevention of Cancer Progression and Recurrence.International journal of molecular and cellular medicine · 2023Review
- FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer.Molecular oncology · 2022Article
- MiR-182-5p Modulates Prostate Cancer Aggressive Phenotypes by Targeting EMT Associated Pathways.Biomolecules · 2022Article
- Racial differences in prostate tumor microenvironment: implications for disparate clinical outcomes and potential opportunities.Cancer health disparities · 2022Article
- PIP5K1α is Required for Promoting Tumor Progression in Castration-Resistant Prostate Cancer.Frontiers in cell and developmental biology · 2022Article
- Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade.International journal of biological sciences · 2022Article
- Emerging Proteins in CRPC: Functional Roles and Clinical Implications.Frontiers in oncology · 2022Review
- Investigation of the Disparities in Ultrasound Imaging Features of miR-323, miR-409-3p, and VEGF Expression Scales in Different Clinicopathological Features of Prostate Carcinoma and Their Correlation with Prognosis.BioMed research international · 2022Article
- Comparison of Androgen Receptor, VEGF, HIF-1, Ki67 and MMP9 Expression between Non-Metastatic and Metastatic Stages in Stromal and Tumor Cells of Oral Squamous Cell Carcinoma.Life (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, no effective targeted therapeutics exists for treatment of metastatic prostate cancer (PCa). Given that matrix metalloproteinases 9 (MMP9) and its associated vascular endothelial growth factor (VEGF) are critical for tumor vascularization and invasion under castration-resistant condition, it is therefore of great importance to define the functional association and interplay between androgen receptor (AR) and MMP9 and their associated key survival and invasion pathways in PCa cells. Here, we found that there was a significant correlation between MMP9 and AR protein expression in primary and metastatic PCa tissues, and a trend that high level of MMP9 expression was associated with poor prognosis. We demonstrated that constitutive activation of AR increased expression of MMP9 and VEGF/VEGF receptors. We further showed that AR exerts its effect on MMP9/VEGF signaling axis through PIP5K1α/AKT. We showed that MMP9 physically interacted with PIP5K1α via formation of protein-protein complexes. Furthermore, elevated expression of MMP9 enhanced ability of AR to activate its target gene cyclin A1. The elevated sequential activation of AR/PIP5K1α/AKT/MMP9/VEGF signaling axis contributed to increased invasiveness and growth of metastatic tumors. Conversely, treatment with PIP5K1α inhibitor significantly suppressed invasiveness of PCa cells expressing constitutively activated AR, this was coincident with its inhibitory effect of this inhibitor on AR/MMP9/VEGF pathways. Our results suggest that AR and MMP9-associated network proteins may be effectively targeted by blocking PIP5K1α/AKT pathways using PIP5K1α inhibitor in metastatic PCa.
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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.