Activation of RIPK2-mediated NOD1 signaling promotes proliferation and invasion of ovarian cancer cells via NF-κB pathway
The goal of this study was to investigate the role and mechanism of action of nucleotide oligomerization domain receptor 1 (NOD1) in ovarian cancer. Results showed that the expressions of NOD1 and receptor interacting serine/threonine kinase 2 (RIPK2) were notably upregulated in non-metastatic and metastatic ovarian tumors compared with matched non-tumor tissues, and their expression in metastatic tumor tissues was higher than that in non-metastatic tumors. Overexpression of NOD1 facilitated the expression of proliferation-related proteins (PCNA and Ki67) and proliferation and invasion of ovarian cancer cells. Overexpression of NOD1 promoted NF-κB expression and phosphorylation. Importantly, NOD1 bound with RIPK2, and silencing of RIPK2 partly rescued the promotion of NOD1 to NF-κB expression and its phosphorylation. The promotion of NOD1 to ovarian cancer cell proliferation and invasion was partly reversed by RIPK2 silencing. Results from our in vivo study indicate that overexpression of NOD1 accelerated the growth of ovarian cancer tumors, expression of proliferation-related proteins, and activation of NF-κB. However, silencing of NOD1 suppressed tumor growth. In summary, NOD1 facilitates ovarian cancer progression by activating NF-κB signaling by binding to RIPK2. We suggest a new strategy for the treatment of ovarian cancer.
