Laboratório de Biologia Do Câncer, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Av. 28 de Setembro, 87 fundos - 4º andar, Vila Isabel, Rio de Janeiro, RJ, CEP: 20551-030, Brazil.
J Cancer Res Clin Oncol. 2021 May;147(5):1287-1297. doi: 10.1007/s00432-021-03552-3. Epub 2021 Feb 12.
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.
We selected and analyzed 80 original articles and reviews from Pubmed that focuses on the study of SAV1 in cancer.
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.
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.
在复杂的肿瘤环境中，了解具有促肿瘤或抗肿瘤作用的蛋白质的功能对于支持癌症临床领域的进展至关重要。其中， salvador 家族 WW 结构域蛋白 1（SAV1）备受关注。这种蛋白质在 Hippo 通路的肿瘤抑制因子方面发挥着重要作用，该通路负责控制细胞增殖、器官大小、发育和组织稳态。然而，该通路的功能失调可能导致肿瘤发生和肿瘤进展。由于 SAV1 是一种肿瘤抑制支架蛋白，我们探讨了 SAV1 与其伴侣共同发挥的功能、其表达的调控及其在各种类型癌症中的抗肿瘤作用。
我们从 Pubmed 中选择并分析了 80 篇重点研究 SAV1 在癌症中作用的原始文章和综述。
SAV1 与几种蛋白质相互作用，具有不同的功能，除了 Hippo 通路之外，还通过其他机制发挥肿瘤抑制作用。SAV1 表达的调节似乎通过 microRNAs 发生，很少通过突变或启动子甲基化发生。它在不同类型的癌症中下调，导致癌症促进和进展，并与预后不良相关。体内模型表明 SAV1 的缺失有助于肿瘤发生。
SAV1 在几种类型的癌症中作为肿瘤抑制因子发挥着重要作用，突出了 SAV1 和 Hippo 通路在癌症中的重要性。因此，鼓励进一步的研究将 SAV1 作为癌症生物学和癌症临床方法中的分子关键部分纳入其中。
