Deubiquitinating enzyme USP9X regulates metastasis and chemoresistance in triple‐negative breast cancer by stabilizing Snail1

Guan, Tangming; Yang, Xiao; Liang, Hui; Chen, Jiayi; Chen, Yan; Zhu, Yingjie; Liu, Tongzheng

doi:10.1002/jcp.30763

Cited by 17 publications

(11 citation statements)

References 31 publications

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“…UCHL1 plays a role in the malignant progression of TNBC by maintaining cell stemness and promoting invasion [30] . Moreover, USP9X inhibitors inhibit TNBC cell migration, invasion and metastasis and increase cell sensitivity to cisplatin and paclitaxel [31] . Moreover, mRNA expression profiling of BRCC3 has been reported in human breast cancer cells, and exogenous BRCC3 expression is associated with delayed death and increased breast cancer cell proliferation [32] .…”

Section: Discussionmentioning

confidence: 99%

The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells

Huang,

Zheng,

et al. 2024

ABBS

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Triple negative breast cancer (TNBC) has a high recurrence rate, metastasis rate and mortality rate. The aim of this study is to identify new targets for the treatment of TNBC. Clinical samples are used for screening deubiquitinating enzymes (DUBs). MDA-MB-231 cells and a TNBC mouse model are used for in vitro and in vivo experiments, respectively. Western blot analysis is used to detect the protein expressions of DUBs, zinc finger E-box binding homeobox 1 (ZEB1), and epithelial-mesenchymal transition (EMT)-related markers. Colony formation and transwell assays are used to detect the proliferation, migration and invasion of TNBC cells. Wound healing assay is used to detect the mobility of TNBC cells. Immunoprecipitation assay is used to detect the interaction between breast cancer susceptibility gene 1/2-containing complex subunit 3 (BRCC3) and Z EB1. ZEB1 ubiquitination levels, protein stability, and protein degradation are also examined. Pathological changes in the lung tissues are detected via HE staining. Our results show a significant positive correlation between the expressions of BRCC3 and ZEB1 in clinical TNBC tissues. Interference with BRCC3 inhibits TNBC cell proliferation, migration, invasion and EMT. BRCC3 interacts with ZEB1 and interferes with BRCC3 to inhibit ZEB1 expression by increasing ZEB1 ubiquitination. Interference with BRCC3 inhibits TNBC cell tumorigenesis and lung metastasis in vivo . In all, this study demonstrates that BRCC3 can increase the stability of ZEB1, upregulate ZEB1 expression, and promote the proliferation, migration, invasion, EMT, and metastasis of TNBC cells, providing a new direction for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells

Huang,

Zheng,

et al. 2024

ABBS

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“…[42][43][44] Stabilizing Snail1 could regulate metastasis and chemoresistance of triple-negative breast cancer by. 45 MKI67 and MMPs could promote the progress of tumor, were the potential biomarker for clinical examination of malignant characteristics in tumors. [46][47][48] Here, we show that DNTTIP1 was associated with EMT in Ss-GSEA and GSEA.…”

Section: Discussionmentioning

confidence: 99%

High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma

Wang¹,

Wei-quan²,

Lou³

et al. 2023

PGPM

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Background Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC. Methods Kaplan–Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC. Results DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC. Conclusion This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.

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“…YAP1 is deubiquitinated and stabilized by USP9X, thereby promoting breast cancer cell survival and resulting in chemotherapy resistance ( 47 ). USP9X stabilizes Snail1, a key factor regulating the EMT process, contributing to metastasis and chemoresistance in triple-negative breast cancer ( 48 ). Furthermore, downregulation of USP9X renders estrogen receptor α-positive breast cancer resistant to tamoxifen, leading to a poor outcome for patients following adjuvant tamoxifen treatment ( 89 ).…”

Section: Roles Of Usp9x In Human Cancermentioning

confidence: 99%

Roles of USP9X in cellular functions and tumorigenesis (Review)

Meng,

Hong,

Yang

et al. 2023

Oncol Lett

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Ubiquitin-specific peptidase 9X (USP9X) is involved in certain human diseases, including malignancies, atherosclerosis and certain diseases of the nervous system. USP9X promotes the deubiquitination and stabilization of diverse substrates, thereby exerting a versatile range of effects on pathological and physiological processes. USP9X serves vital roles in the processes of cell survival, invasion and migration in various types of cancer. The present review aims to highlight the current knowledge of USP9X in terms of its structure and the possible mediatory mechanisms involved in certain types of cancer, providing a thorough introduction to its biological functions in carcinogenesis and further outlining its oncogenic or suppressive properties in a diverse range of cancer types. Finally, several perspectives regarding USP9X-targeted pharmacological therapeutics in cancer development are discussed.

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Deubiquitinating enzyme USP9X regulates metastasis and chemoresistance in triple‐negative breast cancer by stabilizing Snail1

Cited by 17 publications

References 31 publications

The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells

The deubiquitinase BRCC3 increases the stability of ZEB1 and promotes the proliferation and metastasis of triple-negative breast cancer cells

High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma

Roles of USP9X in cellular functions and tumorigenesis (Review)

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