AI Article Synopsis
- Aberrant Wnt signaling and anti-apoptotic mechanisms play crucial roles in cancer, particularly in leukemia and oral squamous cell carcinoma (OSCC), highlighting the importance of the enzyme Paraoxonase-2 (PON2) in these processes.
- Researchers discovered a novel regulation of PON2 through the Wnt/GSK3β/β-catenin pathway, confirmed by various studies, showing a significant connection between PON2 and β-catenin levels in OSCC tissues.
- The findings suggest that elevated PON2 expression is linked to cancer relapse and therapy resistance, proposing PON2 as a potential new biomarker for prognosis and treatment challenges in cancer.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239460 | PMC |
| http://dx.doi.org/10.18632/oncotarget.9013 | DOI Listing |
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