ArticleCell death & disease2013
PIAS1-modulated Smad2/4 complex activation is involved in zinc-induced cancer cell apoptosis.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Multi-omics analysis reveals PIAS family gene dysregulation as a driver of head and neck squamous cell carcinoma (HNSC) progression and therapeutic vulnerability.Discover oncology · 2025Article
- SPOP mutations increase PARP inhibitor sensitivity via CK2/PIAS1/SPOP axis in prostate cancer.JCI insight · 2025Article
- Proteome-wide Mendelian randomization identifies causal plasma proteins in prostate cancer development.Human genomics · 2025Article
- The role of TMEM163 protein in thyroid microcarcinoma: expression pattern and clinical implications.Journal of endocrinological investigation · 2025Article
- Metal-Based Nanomedicines for Inducing Programmed Cell Death to Enhance the Efficacy of Cancer Immunotherapy.International journal of nanomedicine · 2025Review
- Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance.Frontiers in cell and developmental biology · 2022Review
- Article
- The E3 Ligase PIAS1 Regulates p53 Sumoylation to Control Stress-Induced Apoptosis of Lens Epithelial Cells Through the Proapoptotic Regulator Bax.Frontiers in cell and developmental biology · 2021Article
- Advances of Zinc Signaling Studies in Prostate Cancer.International journal of molecular sciences · 2020Review
- Dexamethasone induced apoptosis of A549 cells via the TGF-β1/Smad2 pathway.Oncology letters · 2018Article
- Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2.BMC biology · 2017Article
- DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-β/SMAD4 signaling.Oncogene · 2017Article
- Altholactone Inhibits NF-κB and STAT3 Activation and Induces Reactive Oxygen Species-Mediated Apoptosis in Prostate Cancer DU145 Cells.Molecules (Basel, Switzerland) · 2017Article
- Lymphocytic, cytokine and transcriptomic profiles in peripheral blood of dogs with atopic dermatitis.BMC veterinary research · 2016Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostate cancer is one of the most frequently diagnosed cancers among men. Dietary intake of nutrients is considered crucial for preventing the initiation of events leading to the development of carcinoma. Many dietary compounds have been considered to contribute to cancer prevention including zinc, which has a pivotal role in modulating apoptosis. However, the mechanism for zinc-mediated prostate cancer chemoprevention remains enigmatic. In this study, we investigated the therapeutic effect of zinc in prostate cancer chemoprevention for the first time. Exposure to zinc induced apoptosis and resulted in transactivation of p21(WAF1/Cip1) in a Smad-dependent and p53-independent manner in prostate cancer cells. Smad2 and PIAS1 proteins were significantly upregulated resulting in dramatically increased interactions between Smad2/4 and PIAS1 in the presence of zinc in LNCaP cells. Furthermore, it was found that the zinc-induced Smad4/2/PIAS1 transcriptional complex is responsible for Smad4 binding to SBE1 and SBE3 regions within the p21(WAF1/Cip1) promoter. Exogenous expression of Smad2/4 and PIAS1 promotes zinc-induced apoptosis concomitant with Smad4 nuclear translocation, whereas endogenous Smad2/4 silencing inhibited zinc-induced apoptosis accompanying apparent p21(WAF1/Cip1) reduction. Moreover, the knockdown of PIAS1 expression attenuated the zinc-induced recruitment of Smad4 on the p21(WAF1/Cip1) promoter. The colony formation experiments demonstrate that PIAS1 and Smad2/4 silencing could attenuate zinc apoptotic effects, with a proliferation of promoting effects. We further demonstrate the correlation of apoptotic sensitivity to zinc and Smad4 and PIAS1 in multiple cancer cell lines, demonstrating that the important roles of PIAS1, Smad2, and Smad4 in zinc-induced cell death and p21(WAF1/Cip1) transactivation were common biological events in different cancer cell lines. Our results suggest a new avenue for regulation of zinc-induced apoptosis, and provide a model that demonstrates zinc endorses the Smad2/4/PIAS1 complex to activate the p21(WAF1/Cip1) gene that mediates apoptosis.
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