By restoration assessment, we found that only re-expression of a fully functional Gab1, but not a mutant Gab1 that harbors either Par3 binding-deficiency or Par1b binding-deficiency, could reverse the repressive phenotype of cell migration in vitro and metastasis in vivo due to Gab1 knockdown.
Collectively, our data show that reduced KC Par3 function fosters a permissive P-cadherin-dependent niche for MC transformation, invasion, and metastasis.
Knockdown of Par3 inhibits PCa cell migration and invasion in vitro and tumor metastasis in vivo, whereas overexpression of Par3 yields the opposite results.
Par3 silencing dramatically reduced tumor latency in both models and produced invasive and metastatic tumors that retained epithelial marker expression.
To learn more on the role of PAR1 and PAR3 antagonism in RMS proliferation and metastasis, we knocked down both receptors by using a short hairpin RNA strategy.