PRKAR2B promotes prostate cancer metastasis by activating Wnt/β-catenin and inducing epithelial-mesenchymal transition.

Castration-resistant prostate cancers (CRPC) that occur after the failure of androgen-blocking therapies cause most of the deaths in prostate cancer (PCa) patients. In a previous study we identified that PRKAR2B expression is upregulated in CRPC and possesses potentials to develop CRPC. Here we further investigated the underlying mechanism of PRKAR2B in regulating prostate cancer metastasis. We established an androgen-independent LNCaPcell line (LNCaP-AI), and investigated the function of PRKAR2B on regulating cell invasion in vitro and in vivo. We found that PRKAR2B expression was markedly increased in LNCaP-AI cells and metastatic CRPC (mCRPC) tissues compared to LNCaP cells and primary PCa specimens, respectively. PRKAR2B level was significantly correlated with the Gleason score and lymph nodes metastasis in PCa. In vitro, PRKAR2B overexpression promoted cell invasion, whereas knockdown of PRKAR2B in CRPC cells inhibited cell invasion. PRKAR2B overexpression also promoted tumor metastasis in vivo. PRKAR2B resulted in a decreased expression of E-cadherin and an increased expression of Vimentin, N-cadherin, Fibronectin, indicating that PRKAR2B induced epithelial-mesenchymal transition (EMT). PRKAR2B activated Wnt/β-catenin signaling in CRPC cells. More important, inhibition of Wnt/β-catenin attenuated PRKAR2B-induced EMT and cancer cells invasion. Our results provided novel insights to PRKAR2B-driven CRPC cell invasion and indicated that PRKAR2B might be served as a potential target for CRPC therapy.

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