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

Amorim, Ísis Salviano Soares de; Rodrigues, Mariana Moreno de Sousa; Mencalha, André Luiz

doi:10.1007/s00432-021-03552-3

Cited by 9 publications

(4 citation statements)

References 86 publications

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“…Although Wang et al [32] demonstrated that SAV1 was silenced by DNA methylation in the AsPC-1 and SW1990 pancreatic cancer cell lines, many other studies have shown that the regulation of SAV1 expression by DNA methylation or mutation is not common in cancer [8,[33][34][35][36][37]. Some authors suggested that MST2-mediated phosphorylation of the SAV1 protein stabilizes this protein and increases the interaction of SAV1 with MST2, which, in turn, increases the levels of these proteins.…”

Section: Discussionmentioning

confidence: 99%

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Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer

Kowalczyk,

Krazinski,

Piotrowska

et al. 2023

Cancers

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Salvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. This study aimed to examine the expression level of the SAV1 gene in colorectal cancer (CRC) and its prognostic value and associations with tumor progression. We obtained matched pairs of tumor tissue and non-cancerous mucosa of the large intestine from 94 CRC patients as well as 40 colon biopsies of healthy subjects collected during screening colonoscopy. The tissue samples and CRC cell lines were quantified for SAV1 mRNA levels using the quantitative polymerase chain reaction method, while SAV1 protein expression was estimated in the paired tissues of CRC patients using immunohistochemistry. The average level of SAV1 mRNA was decreased in 93.6% of the tumor tissues compared to the corresponding non-cancerous tissues and biopsies of healthy colon mucosa. A downregulated expression of SAV1 mRNA was also noted in the CRC cell lines. Although the average SAV1 immunoreactivity was increased in the CRC samples compared to the non-cancerous tissues, a decreased immunoreactivity of the SAV1 protein in the tumor specimens was associated with lymph node involvement and higher TNM disease stage and histological grade. The results of our study suggest that the impaired expression of SAV1 is involved in CRC progression.

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Section: Discussionmentioning

confidence: 99%

“…It is encoded by the SAV1 gene, whose chromosomal location is 14q22.1. SAV1 consists of two WW domains and one coiled-coil domain in the C-terminal region that are reported in proteins whose major feature is to act as a scaffold [8]. It has been noted that SAV1 also plays an antitumor role, independent of the Hippo pathway [9].…”

Section: Introductionmentioning

confidence: 99%

Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer

Kowalczyk,

Krazinski,

Piotrowska

et al. 2023

Cancers

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“…SAV1, expressed in several human cell lines and located in the cell cytoplasm and nucleus, is a core kinase component of the Hippo signaling pathway [ 40 ]. It plays an extensive and prominent role in the inhibition of tumorigenesis, mainly through the Hippo pathway in various cancers, including CRC, breast, pancreatic, kidney, lung cancer, and so on [ 41 ]. RORC is a member of the nuclear orphan receptor family and performs critical regulatory functions in cell growth, metastasis, chemoresistance, and the negative regulation of PD-L1 expression in various cancers [ 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Tumor Antigens and Immune Subtypes of Malignant Mesothelioma for mRNA Vaccine Development

Wang

Yang

et al. 2022

Vaccines

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Background: mRNA-based cancer vaccines have been considered a promising anticancer therapeutic approach against various cancers, yet their efficacy for malignant mesothelioma (MESO) is still not clear. The present study is designed to identify MESO antigens that have the potential for mRNA vaccine development, and to determine the immune subtypes for the selection of suitable patients. Methods: A total of 87 MESO datasets were used for the retrieval of RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA) databases. The possible antigens were identified by a survival and a genome analysis. The samples were divided into two immune subtypes by the application of a consensus clustering algorithm. The functional annotation was also carried out by using the DAVID program. Furthermore, the characterization of each immune subtype related to the immune microenvironment was integrated by an immunogenomic analysis. A protein–protein interaction network was established to categorize the hub genes. Results: The five tumor antigens were identified in MESO. FAM134B, ALDH3A2, SAV1, and RORC were correlated with superior prognoses and the infiltration of antigen-presenting cells (APCs), while FN1 was associated with poor survival and the infiltration of APCs. Two immune subtypes were identified; TM2 exhibited significantly improved survival and was more likely to benefit from vaccination compared with TM1. TM1 was associated with a relatively quiet microenvironment, high tumor mutation burden, and enriched DNA damage repair pathways. The immune checkpoints and immunogenic cell death modulators were also differentially expressed between two subtypes. Finally, FN1 was identified to be the hub gene. Conclusions: FAM134B, ALDH3A2, SAV1, RORC, and FN1 are considered as possible and effective mRNA anti-MESO antigens for the development of an mRNA vaccine, and TM2 patients are the most suitable for vaccination.

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“…Although previous studies have implicated YAP in the progression of arthritis, there are still some important connections that need to be established, such as changes in YAP activity across different species of FLSs, the correlation between altered YAP activity and abnormal proliferation of FLSs, and the mechanisms by which upstream pro-inflammatory factors regulate YAP. SAV1, a known tumor suppressor in various cancer types, exhibits downregulation in cancerous tissues or cells, thereby promoting tumor progression, cancer aggressiveness, and unfavorable prognosis 8 , 12 . However, SAV1 downregulation has not been investigated in RA, with the mechanism of expression and regulation of SAV1 in many diseases including RA remaining ambiguous.…”

Section: Introductionmentioning

confidence: 99%

GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis

Guo,

Jiang,

Chu

et al. 2024

Acta Pharmaceutica Sinica B

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

Cited by 9 publications

References 86 publications

Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer

Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer

Identification of Tumor Antigens and Immune Subtypes of Malignant Mesothelioma for mRNA Vaccine Development

GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis

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