ArticleCancer letters2022
Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases.
Article in Cancer letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Bone Metastatic Progression of Prostate Cancer Is Regulated by TRIM28-LDHA-Mediated Metabolism.Molecular cancer research : MCR · 2026Article
- Review
- Bone Effects of Anti-Cancer Treatments in 2024.Calcified tissue international · 2025Review
- ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy.Materials today. Bio · 2025Article
- Osteoblast-Derived ECM1 Promotes Anti-Androgen Resistance in Bone Metastatic Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ELOVL2 mediated stabilization of AR contributes to enzalutamide resistance in prostate cancer.Frontiers in cell and developmental biology · 2025Article
- MiR-20a-5p Targeting theAnimals : an open access journal from MDPI · 2024Article
- MiR26a reverses enzalutamide resistance in a bone-tumor targeted system with an enhanced effect on bone metastatic CRPC.Journal of nanobiotechnology · 2024Article
- Tumor removal limits prostate cancer cell dissemination in bone and osteoblasts induce cancer cell dormancy through focal adhesion kinase.Journal of experimental & clinical cancer research : CR · 2023Article
- Parathyroid Hormone-Related Protein/Parathyroid Hormone Receptor 1 Signaling in Cancer and Metastasis.Cancers · 2023Review
- Pleckstrin homology (PH) domain and Leucine Rich Repeat Phosphatase 1 (Phlpp1) Suppresses Parathyroid Hormone Receptor 1 (Pth1r) Expression and Signaling During Bone Growth.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Enzalutamide resistance has been observed in approximately 50% of patients with prostate cancer (PCa) bone metastases. Therefore, there is an urgent need to investigate the mechanisms and develop strategies to overcome resistance. We observed enzalutamide resistance in bone lesion development induced by PCa cells in mouse models. We found that the bone microenvironment was indispensable for enzalutamide resistance because enzalutamide significantly inhibited the growth of subcutaneous C4-2B tumors and the proliferation of C4-2B cells isolated from the bone lesions, and the resistance was recapitulated only when C4-2B cells were co-cultured with osteoblasts. In revealing how osteoblasts contribute to enzalutamide resistance, we found that enzalutamide decreased TGFBR2 protein expression in osteoblasts, which was supported by clinical data. This decrease was possibly through PTH1R-mediated endocytosis. We showed that PTH1R blockade rescued enzalutamide-mediated decrease in TGFBR2 levels and enzalutamide responses in C4-2B cells that were co-cultured with osteoblasts. This is the first study to reveal the contribution of the bone microenvironment to enzalutamide resistance and identify PTH1R as a feasible target to overcome the resistance in PCa bone metastases.
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