ArticleEndocrine-related cancer2012
Nuclear localization of parathyroid hormone-related peptide confers resistance to anoikis in prostate cancer cells.
Article in Endocrine-related cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castration-resistant prostate cancer: dose-related immune boosting and suppression.Cancer immunology, immunotherapy : CII · 2015Trial
- Metabolic reprogramming and signaling adaptations in anoikis resistance: mechanisms and therapeutic targets.Molecular and cellular biochemistry · 2025Review
- Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.Cancers · 2023Review
- Integrated bioinformatics analysis of differentially expressed genes in the temporomandibular joint internal derangement.Clinical and experimental dental research · 2023Article
- An anoikis-related gene signature for prediction of the prognosis in prostate cancer.Frontiers in oncology · 2023Article
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- Survival analysis of multiple peptide vaccination for the selection of correlated peptides in urological cancers.Cancer science · 2018Article
- Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1.International journal of molecular sciences · 2018Article
- Fatty Acids and Calcium Regulation in Prostate Cancer.Nutrients · 2018Review
- Osteoblasts Are the Centerpiece of the Metastatic Bone Microenvironment.Endocrinology and metabolism (Seoul, Korea) · 2016Review
- Intrinsic cellular signaling mechanisms determine the sensitivity of cancer cells to virus-induced apoptosis.Scientific reports · 2016Article
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- Parathyroid hormone-related protein serves as a prognostic indicator in oral squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2014Article
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- Parathyroid hormone-related protein drives a CD11b+Gr1+ cell-mediated positive feedback loop to support prostate cancer growth.Cancer research · 2013Article
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- Parathyroid hormone-related protein: an update.The Journal of clinical endocrinology and metabolism · 2012Review
- The multifaceted actions of PTHrP in skeletal metastasis.Future oncology (London, England) · 2012Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Prostate cancer remains a leading cause of cancer-related death in men, largely attributable to distant metastases, most frequently to bones. Despite intensive investigations, molecular mechanisms underlying metastasis are not completely understood. Among prostate cancer-derived factors, parathyroid hormone-related peptide (PTHrP), first discovered as an etiologic factor for malignancy-induced hypercalcemia, regulates many cellular functions critical to tumor growth, angiogenesis, and metastasis. In this study, the role of PTHrP in tumor cell survival from detachment-induced apoptosis (i.e. anoikis) was investigated. Reduction of PTHLH (encoding PTHrP) gene expression in human prostate cancer cells (PC-3) increased the percentage of apoptotic cells when cultured in suspension. Conversely, overexpression of PTHrP protected prostate cancer cells (Ace-1 and LNCaP, both typically expressing low or undetectable basal PTHrP) from anoikis. Overexpression of nuclear localization signal (NLS)-defective PTHrP failed to protect cells from anoikis, suggesting that PTHrP-dependent protection from anoikis is an intracrine event. A PCR-based apoptosis-related gene array showed that detachment increased expression of the TNF gene (encoding the proapoptotic protein tumor necrosis factor-α) fourfold greater in PTHrP-knockdown PC-3 cells than in control PC-3 cells. In parallel, TNF gene expression was significantly reduced in PTHrP-overexpressing LNCaP cells, but not in NLS-defective PTHrP overexpressing LNCaP cells, when compared with control LNCaP cells. Subsequently, in a prostate cancer skeletal metastasis mouse model, PTHrP-knockdown PC-3 cells resulted in significantly fewer metastatic lesions compared to control PC-3 cells, suggesting that PTHrP mediated antianoikis events in the bloodstream. In conclusion, nuclear localization of PTHrP confers prostate cancer cell resistance to anoikis, potentially contributing to prostate cancer metastasis.
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