SummaryProtease-activated receptor1 (PAR 1 ) is the first and prototype member of an established PAR family comprising four members. The role of PAR 1 in tumor biology has been established, and is characterized by a consistent direct correlation between overexpression of its levels and epithelial tumor aggressiveness. We have found that high expression of the human Par 1 (hPar 1 ) gene in epithelial tumors is controlled largely at the transcriptional level. This led us to assign Egr-1, a transcription activator, as an inducer of hPar 1 , and p53, a tumor suppressor gene, as an inhibitor, both acting to achieve fine tuning of hPar 1 in prostate carcinoma. High PAR 1 levels maintain prosurvival signals in tumor cells while silencing or ablation of the gene induce apoptosis. Studies of our hPar 1 transgenic mice, which overexpress hPar 1 in the mammary glands, revealed a novel PAR 1 -induced b-catenin stabilization function. The components connecting PAR 1 to b-catenin stabilization have been determined, assigning at first G a13 as a selective immediate component. The PAR 1 -G a13 axis recruits disheveled (DVL), an upstream signaling partner of the canonical Wnt signaling pathway. Silencing of DVL by siRNA-DVL potently abrogates PAR 1 -induced b-catenin stabilization, demonstrating its critical role in the process. We, thus, propose that transcriptional regulation of hPar 1 gene over expression in epithelia malignancies initiates a novel signaling pathway, directly connecting to b-catenin stabilization, a core event in both tumorigenesis and developmental processes.