ArticleJournal of experimental & clinical cancer research : CR2023
Targeting PHB1 to inhibit castration-resistant prostate cancer progression in vitro and in vivo.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Unraveling the Mechanism of Perillyl Alcohol and Its Derivatives as Potent Antifungal Agents against Gray Mold.Journal of agricultural and food chemistry · 2026Article
- Targeting NXPH4/ALDH1L2 signaling suppresses enzalutamide resistance in prostate cancer.Cell death discovery · 2026Article
- PHB1 Attenuates Triptolide-induced Cardiotoxicity by Regulating Mitochondrial Dynamics in Cultured Newborn Mice Cardiomyocytes.Journal of cardiovascular pharmacology · 2026Article
- Emerging roles of prohibitins in cancer: an update.Cancer gene therapy · 2025Review
- Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors.International journal of biological sciences · 2025Review
- Reciprocal regulation between RACGAP1 and AR contributes to endocrine therapy resistance in prostate cancer.Cell communication and signaling : CCS · 2024Article
- PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer.Journal of experimental & clinical cancer research : CR · 2024Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCastration-resistant prostate cancer (CRPC) is currently the main challenge for prostate cancer (PCa) treatment, and there is an urgent need to find novel therapeutic targets and drugs. Prohibitin (PHB1) is a multifunctional chaperone/scaffold protein that is upregulated in various cancers and plays a pro-cancer role. FL3 is a synthetic flavagline drug that inhibits cancer cell proliferation by targeting PHB1. However, the biological functions of PHB1 in CRPC and the effect of FL3 on CRPC cells remain to be explored.
methodsSeveral public datasets were used to analyze the association between the expression level of PHB1 and PCa progression as well as outcome in PCa patients. The expression of PHB1 in human PCa specimens and PCa cell lines was examined by immunohistochemistry (IHC), qRT-PCR, and Western blot. The biological roles of PHB1 in castration resistance and underlying mechanisms were investigated by gain/loss-of-function analyses. Next, in vitro and in vivo experiments were conducted to investigate the anti-cancer effects of FL3 on CRPC cells as well as the underlying mechanisms.
resultsPHB1 expression was significantly upregulated in CRPC and was associated with poor prognosis. PHB1 promoted castration resistance of PCa cells under androgen deprivation condition. PHB1 is an androgen receptor (AR) suppressive gene, and androgen deprivation promoted the PHB1 expression and its nucleus-cytoplasmic translocation. FL3, alone or combined with the second-generation anti-androgen Enzalutamide (ENZ), suppressed CRPC cells especially ENZ-sensitive CRPC cells both in vitro and in vivo. Mechanically, we demonstrated that FL3 promoted trafficking of PHB1 from plasma membrane and mitochondria to nucleus, which in turn inhibited AR signaling as well as MAPK signaling, yet promoted apoptosis in CRPC cells.
conclusionOur data indicated that PHB1 is aberrantly upregulated in CRPC and is involved in castration resistance, as well as providing a novel rational approach for treating ENZ-sensitive CRPC.
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