ArticleOncogene2019
FDPS cooperates with PTEN loss to promote prostate cancer progression through modulation of small GTPases/AKT axis.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
- Article
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- Estrogen-Dependent Regulation of FDPS in the Mouse Uterus and Its Expression in Endometrial Cancer.International journal of molecular sciences · 2026Article
- Taxodione Inhibits Glioblastoma Proliferation and Potentiates the Cytotoxicity of Paclitaxel.ACS chemical biology · 2025Article
- Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer.Oncogene · 2025Article
- Androgen Signaling in Prostate Cancer: When a Friend Turns Foe.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Article
- Mevalonate pathway inhibition reduces bladder cancer metastasis by modulating RhoB protein stability and integrin β1 localization.Communications biology · 2024Article
- Article
- Understanding the function of Pax5 in development of docetaxel-resistant neuroendocrine-like prostate cancers.Cell death & disease · 2024Article
- Engineered Immunologic Niche Monitors Checkpoint Blockade Response and Probes Mechanisms of Resistance.Immunomedicine · 2024Article
- Modulation of the RAC1/MAPK/ERK signalling pathway by farnesyl diphosphate synthase regulates granulosa cells proliferation in polycystic ovary syndrome.Human cell · 2024Article
- Identifying squalene epoxidase as a metabolic vulnerability in high-risk osteosarcoma using an artificial intelligence-derived prognostic index.Clinical and translational medicine · 2024Article
- DNA Repair Enzyme XRCC4 30 bp Indel Intron 3 Locus Significant Association with Predisposition of Cataract in Senility.Applied biochemistry and biotechnology · 2024Article
- Identification of novel targets associated with cholesterol metabolism in nonalcoholic fatty liver disease: a comprehensive study using Mendelian randomization combined with transcriptome analysis.Frontiers in genetics · 2024Article
- Understanding the role of Pax5 in development of taxane-resistant neuroendocrine like prostate cancers.Research square · 2023Article
- Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo.Journal of ovarian research · 2023Article
- Cholesterol Metabolism in Pancreatic Cancer.Cancers · 2023Review
- Potent FOXO3a Activators from Biologically Active Compound Library for Cancer Therapeutics: An in silico Approach.Applied biochemistry and biotechnology · 2023Article
- Farnesyl diphosphate synthase promotes cell proliferation by regulating gene expression and alternative splicing profiles in HeLa cells.Oncology letters · 2023Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Farnesyl diphosphate synthase (FDPS), a mevalonate pathway enzyme, is highly expressed in several cancers, including prostate cancer (PCa). To date, the mechanistic, functional, and clinical significance of FDPS in cancer remains unexplored. We evaluated the FDPS expression and its cancer-associated phenotypes using in vitro and in vivo methods in PTEN-deficient and sufficient human and mouse PCa cells and tumors. Interestingly, FDPS overexpression synergizes with PTEN deficiency in PTEN conditionally knockout mice (P < 0.05) and expressed significantly higher in human (P < 0.001) PCa tissues, cell lines, and murine tumoroids compared to respective controls. In silico analysis revealed that FDPS is associated with increasing Gleason score, PTEN functionally deficient status, and poor survival of PCa. Ectopic overexpression of FDPS promotes oncogenic phenotypes such as colony formation (P < 0.01) and proliferation (P < 0.01) through activation of AKT and ERK signaling by prenylating Rho A, Rho G, and CDC42 small GTPases. Of interest, knockdown of FDPS in PCa cells exhibits decreased colony growth and proliferation (P < 0.001) by modulating AKT and ERK pathways. Further, genetic and pharmacological inhibition of PI3K but not AKT reduced FDPS expression. Pharmacological targeting of FDPS by zoledronic acid (ZOL), which is already in clinics, exhibit reduced growth and clonogenicity of human and murine PCa cells (P < 0.01) and 3D tumoroids (P < 0.02) by disrupting AKT and ERK signaling through direct interference of small GTPases protein prenylation. Thus, FDPS plays an oncogenic role in PTEN-deficient PCa through GTPase/AKT axis. Identifying mevalonate pathway proteins could serve as a therapeutic target in PTEN dysregulated tumors.
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