ArticleOncotarget2016
The anti-apoptotic PON2 protein is Wnt/β-catenin-regulated and correlates with radiotherapy resistance in OSCC patients.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Upregulation of paraoxonase-2 enzyme in human osteosarcoma and its involvement in mechanisms promoting the aggressive behavior of tumor cells.Molecular biology reports · 2026Article
- Role of paraoxonase 2 (PON2) as a potential biomarker and therapeutic target in cancer treatment.Journal of cancer research and clinical oncology · 2025Review
- Review
- Investigation of the Molecular Mechanisms of Paraoxonase-2 Mediated Radiotherapy and Chemotherapy Resistance in Oral Squamous Cell Carcinoma.Clinical and translational science · 2025Review
- Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.Cells · 2024Review
- Antiapoptotic PON2 expression and its clinical implications in locally advanced oral squamous cell carcinoma.Cancer science · 2024Article
- Contribution of the Paraoxonase-2 Enzyme to Cancer Cell Metabolism and Phenotypes.Biomolecules · 2024Review
- Paraoxonase-2 expression in oral squamous cell carcinoma.Human cell · 2023Article
- Paraoxonase-2 is upregulated in triple negative breast cancer and contributes to tumor progression and chemoresistance.Human cell · 2023Article
- Application of nano-radiosensitizers in combination cancer therapy.Bioengineering & translational medicine · 2023Review
- Integration of clinical and spatial data to explore lipid metabolism-related genes for predicting prognosis and immune microenvironment in gliomas.Functional & integrative genomics · 2023Article
- Role Played by Paraoxonase-2 Enzyme in Cell Viability, Proliferation and Sensitivity to Chemotherapy of Oral Squamous Cell Carcinoma Cell Lines.International journal of molecular sciences · 2022Article
- Article
- Insights into the role of paraoxonase 2 in human pathophysiology.Journal of biosciences · 2022Article
- Human Paraoxonase-2 (PON2): Protein Functions and Modulation.Antioxidants (Basel, Switzerland) · 2021Review
- Evidence for AJUBA-catenin-CDH4-linked differentiation resistance of mesenchymal stem cells implies tumorigenesis and progression of head and neck squamous cell carcinoma: a single-cell transcriptome approach.Blood and genomics · 2021Article
- Application of Radiosensitizers in Cancer Radiotherapy.International journal of nanomedicine · 2021Review
- Knockdown of LINC00662 represses AK4 and attenuates radioresistance of oral squamous cell carcinoma.Cancer cell international · 2020Article
- The clinical and prognostic significance of paraoxonase-2 in gastric cancer patients: immunohistochemical analysis.Human cell · 2019Article
- Paraoxonases Activities and Polymorphisms in Elderly and Old-Age Diseases: An Overview.Antioxidants (Basel, Switzerland) · 2019Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant Wnt signaling and control of anti-apoptotic mechanisms are pivotal features in different types of cancer to undergo cell death programs. The intracellular human enzyme Paraoxonase-2 (PON2) is known to have anti-apoptotic properties in leukemia and oral squamous cell cancer (OSCC) cells. However, the distinct regulating pathways are poorly understood. First, we present a so far unknown regulation of PON2 protein expression through the Wnt/GSK3β/β-catenin pathway in leukemia and OSCC cells. This was confirmed via in silico analysis, promoter reporter studies and treatment of multiple cell lines (K562, SCC-4, PCI-13) with different Wnt ligands/inhibitors in vitro. Ex vivo analysis of OSCC patients revealed a correlation between PON2 and β-catenin expression in tumor tissue. Higher PON2 expression in OSCC is associated with relapse independently of treatment (e.g. surgery/radio-/chemotherapy). These results emphasize the clinical impact of the newly described regulation of PON2 through Wnt/GSK3β/β-catenin. More importantly, the study revealed the fundamental finding of an overall Wnt/GSK3β/β-catenin dependent regulation of PON2 in different cancers, which was confirmed by systematic and multimethodological approaches. Thus, the herein presented mechanistic insight contributes to a better understanding of tumor specific escape from cell death strategies and suggests PON2 as a new potential biomarker for therapy resistance or as a prognostic tumor marker.
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