The tumor suppressor role of salvador family WW domain-containing protein 1 (SAV1): one of the key pieces of the tumor puzzle.

PURPOSE: In the complex tumor scenario, understanding the function of proteins with protumor or antitumor roles is essential to support advances in the cancer clinical area. Among them, the salvador family WW domain-containing protein 1 (SAV1) is highlighted. This protein plays a fundamental role in the tumor suppressor face of the Hippo pathway, which are responsible for controlling cell proliferation, organ size, development and tissue homeostasis. However, the functional dysregulation of this pathway may contribute to tumorigenesis and tumor progression. As SAV1 is a tumor suppressor scaffold protein, we explored the functions performed by SAV1 with its partners, the regulation of its expression, and its antitumor role in various types of cancer. METHODS: We selected and analyzed 80 original articles and reviews from Pubmed that focuses on the study of SAV1 in cancer. RESULTS: SAV1 interacts with several proteins, has different functions and acts as tumor suppressor by other mechanisms besides Hippo pathway. SAV1 expression regulation seems to occur by microRNAs and rarely by mutation or promoter methylation. It is downregulated in different types of cancer, which leads to cancer promotion and progression and is associated with poor prognosis. In vivo models have shown that the loss of SAV1 contributes to tumorigenesis. CONCLUSION: SAV1 plays a relevant role as tumor suppressor in several types of cancer, highlighting SAV1 and the Hippo pathway's importance to cancer. Thus, encouraging further studies to include the SAV1 as a molecular key piece in cancer biology and in clinical approaches to cancer.