SYCP3 enhances prostate cancer metastasis and modulates the DNA damage response pathway
TL;DR
Biological validation analyses showed that SYCP3 depletion significantly reduced the invasive and migratory abilities of DU145 cells and increased their adhesion capacity, suggesting a role for SYCP3 in DNA damage response and genomic instability in PCa metastasis.
Abstract
Prostate cancer (PCa) is a prevalent male cancer with high survival rates, except in advanced or metastatic stages, for which effective treatments are lacking. Metastatic PCa involves complex mechanisms including loss of tumor suppressor genes and DNA repair molecules, which impacts therapy responses. Analyses of tumor samples demonstrated that SYCP3 expression is frequently upregulated in PCa tumors from patients in advanced stages. Due to the implication of SYCP3 on DNA repair processes, we have analyzed the role of SYCP3 on the cellular response to radiotherapy (RT) and found that its depletion induced RT resistance, suggesting a role for SYCP3 in DNA damage response and genomic instability. Additionally, based on a previous CRISPR/Cas9 genome-wide screening identifying SYCP3 as a potential regulator of metastatic invasion in DU145 PCa cells, we performed biological validation analyses, which showed that SYCP3 depletion significantly reduced the invasive and migratory abilities of DU145 cells and increased their adhesion capacity. All these data support a role for SYCP3 in PCa metastasis and provides opportunities for personalized medicine.