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Protein salvador homolog 1 (SAV1) is a critical scaffold protein within the Hippo signaling pathway, essential for regulating organ size and suppressing tumor growth (UniProt Q9H4B6). It functions by facilitating the interaction between MST1/2 kinases and LATS1/2 kinases, which leads to the phosphorylation and subsequent inactivation of the transcriptional co-activators YAP and TAZ (PubMed: 29063833). Downregulation or loss of SAV1 mRNA and protein is frequently observed in various malignancies, including colorectal, renal, and pancreatic cancers, where it results in uncontrolled cell proliferation and resistance to apoptosis (PMC5835901). Therapeutic strategies focusing on SAV1 mRNA often involve restoring its expression through gene therapy or mRNA-based delivery systems to reactivate the Hippo pathway's tumor-suppressive functions (PubMed: 33654091). As a key regulator of cellular homeostasis, SAV1 serves as both a potential therapeutic target and a prognostic biomarker in oncology. Its role extends beyond the Hippo pathway to include interactions with Akt and the Wnt signaling pathway, further influencing cell survival and polarity (PubMed: 28087714).
Restoration of Hippo pathway signaling to inhibit YAP/TAZ oncogenic activity and promote apoptosis in tumor cells.
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