Overexpression of the Ubiquitin Specific Proteases USP43, USP41, USP27x and USP6 in Osteosarcoma Cell Lines: Inhibition of Osteosarcoma Tumor Growth and Lung Metastasis Development by the USP Antagonist PR619

Lavaud, Mélanie; Mullard, Mathilde; Tesfaye, Robel; Amiaud, Jérôme; Legrand, Mélanie; Danieau, Geoffroy; Brion, Régis; Morice, Sarah; Regnier, Laura; Dupuy, Maryne; Royer, Bénédicte Brounais-Le; Lamoureux, François; Ory, Benjamin; Rédini, Françoise; Verrecchia, Franck

doi:10.3390/cells10092268

Cited by 22 publications

(18 citation statements)

References 50 publications

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“…Recent studies have analyzed overall survival of cancer patients according to expression of USP41 based on The Cancer Genome Atlas (TCGA) database and suggested USP41 as marker predicting prognosis especially in invasive breast cancer and lung cancer [ 23 , 24 ]. Even though some researchers have reported that USP41 promotes cancer cell migration and proliferation [ 25 , 26 ], the underlying specific mechanism to cancer migration and EMT is still unclear.…”

Section: Introductionmentioning

confidence: 99%

USP41 Enhances Epithelial–Mesenchymal Transition of Breast Cancer Cells through Snail Stabilization

Yoon

Seo

Woo

et al. 2023

IJMS

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Ubiquitination, one of many post-translational modifications, causes proteasome-mediated protein degradation by attaching ubiquitin to target proteins. Multiple deubiquitinases inhibit the ubiquitination pathway by removing the ubiquitin chain from protein, thus contributing to the stabilization of substrates. USP41 contributes to invasion, apoptosis and drug resistance in breast and lung cancer cells. However, the detailed mechanism and role of USP41 in breast cancer have not been elucidated. USP41 was overexpressed and showed poor prognosis according to the aggressive phenotype of breast cancer cells. Knockdown of USP41 inhibited migration and growth of breast cancer cells, whereas overexpression of USP41 increased cell growth and migration. In addition, depletion of USP41 downregulated Snail protein expression, an epithelial–mesenchymal transition marker, but not mRNA expression. Furthermore, USP41 interacted with and inhibited ubiquitination of Snail, resulting in the increase in Snail stabilization. Therefore, these data demonstrated that USP41 increases migration of breast cancer cells through Snail stabilization.

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Section: Introductionmentioning

confidence: 99%

USP41 Enhances Epithelial–Mesenchymal Transition of Breast Cancer Cells through Snail Stabilization

Yoon

Seo

Woo

et al. 2023

IJMS

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“…Patients with PDAC have a poor prognosis, highlighting the need to develop innovative therapeutic strategies for this aggressive illness [25]. USPs are the largest DUBs family and a growing number of studies show that various USPs may be important targets for cancer therapy due to their ability to regulate tumor formation, including tumor growth and the process of metastasis [16,17,19,20,[26][27][28]. Previous research indicates that USP43, a member of the USPs family, plays a significant role in breast cancer, CRC, lung squamous cell carcinoma, and nonsmall cell lung cancer can promotes tumor migration, invasion, and associated with a poor prognosis [22,[29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-Specific Protease 43 Impacts Pancreatic Ductal Adenocarcinoma Prognosis by Altering Its Proliferation and Infiltration of Surrounding Immune Cells

Zhao

Lin

Guo

et al. 2023

Journal of Immunology Research

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Background. Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer, and the therapy options for PDAC remain restricted. The distinctive tumor immunological microenvironment (TIME) of PDAC, comprising a high number of stromal cells and a limited infiltration of cytotoxic T lymphocytes (CTLs), rendered immunotherapy ineffective. The protein level of ubiquitin-specific protease 43 (USP43) was a prognostic predictor in numerous cancers; however, its function in PDAC is limited. This article focuses on the influence of USP43 expression on PDAC prognosis and TIME alteration. Methods. Based on TCGA database and tissue microarray staining, the expression of USP43 in PDAC was evaluated. The association between USP43 and prognosis was then investigated using tissue samples and online databases. In PDAC tumor tissues, the correlation between USP43 expression and clinicopathological characteristics, immune cell infiltration, and prognosis was investigated. The expression of USP43 in PDAC cell lines was evaluated using quantitative polymerase chain reaction. Using a cell counting kit-8 (CCK-8) and a cell colony formation test, the viability of the cells was determined. On the basis of online databases and tissue samples, the link between USP43 and immune cell infiltration around PDAC was also examined. For statistical analyses, the software GraphPad, R, and SPSS 26.0 were utilized. Results. The expression of USP43 was considerably higher in PDAC compared to normal pancreatic tissue in both the TCGA database and the tissue microarrays of PDAC patients ( P < 0.001 ). High USP43 expression was associated with poor overall survival in both the TCGA database and the tissue microarray of PDAC patients ( P = 0.046 and 0.021, respectively). USP43 overexpression promoted PANC-1 cell proliferation ( P = 0.0018 ), but USP43 knockdown decreased PANC02 cell proliferation ( P < 0.001 ). According to the TCGA database, USP43 is associated with T cell activation and inhibits CD8+ T cell activation in PDAC, as proven by a study of cell lines. Moreover, in both TCGA and PDAC cell lines, USP43 expression was negatively linked with the chemokine signaling pathway. Conclusions. Overexpression of USP43 is a potential prognostic indicator for PDAC patients. USP43 is a potential biomarker associated with T cell activation, suppression of CD8+ T cell enrichment, and the cytokine signal pathway. Future multicenter studies are needed to confirm our findings and their potential application in the treatment of PDAC patients.

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“…Through statistical studies, Lavaud et al. found that patients with highly expressed USP6 and USP41 had significantly decreased survival ( 100 ). BRCA1-associated protein-1 (BAP1), an important nucleus-associated deubiquitinating enzyme, was significantly decreased in osteosarcoma, and was able to affect metastasis and invasion of osteosarcoma cells by regulating the PI3K/AKT pathway ( 101 ).…”

Section: Ubiquitination/deubiquitination In Osteosarcomamentioning

confidence: 99%

Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma

et al. 2022

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Although some advances have been made in the treatment of osteosarcoma in recent years, surgical resection remains the mainstream treatment. Initial and early diagnosis of osteosarcoma could be very difficult to achieve due to the insufficient sensitivity for the means of examination. The distal metastasis of osteosarcoma also predicts the poor prognosis of osteosarcoma. In order to solve this series of problems, people begin to discover a new method of diagnosing and treating osteosarcoma. Ubiquitination, as an emerging posttranslational modification, has been shown to be closely related to osteosarcoma in studies over the past decades. In general, this review describes the cellular functions and molecular mechanisms of ubiquitination during the development of osteosarcoma.

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Overexpression of the Ubiquitin Specific Proteases USP43, USP41, USP27x and USP6 in Osteosarcoma Cell Lines: Inhibition of Osteosarcoma Tumor Growth and Lung Metastasis Development by the USP Antagonist PR619

Cited by 22 publications

References 50 publications

USP41 Enhances Epithelial–Mesenchymal Transition of Breast Cancer Cells through Snail Stabilization

USP41 Enhances Epithelial–Mesenchymal Transition of Breast Cancer Cells through Snail Stabilization

Ubiquitin-Specific Protease 43 Impacts Pancreatic Ductal Adenocarcinoma Prognosis by Altering Its Proliferation and Infiltration of Surrounding Immune Cells

Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma

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