Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation

Wu, Yadi; Wang, Yu; Lin, Yiwei; Liu, Yajuan; Wang, Yifan; Jia, Jianhang; Singh, Puja; Chi, Young‐In; Wang, Chi; Dong, Chenfang; Li, Wei; Tao, Min; Napier, Dana; Shi, Qiuying; Deng, Jiong; Evers, B. Mark; Zhou, Binhua P.

doi:10.1038/ncomms14228

Cited by 105 publications

(112 citation statements)

References 65 publications

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“…Expression of Dub3 blocked Snail degradation mediated by the E3 ligases Fbxl14 and Fbxw1/β-TRCP1 [38] . Functionally, we found that the expression of Dub3 in breast cancer cell lines not only downregulates markers of luminal type of breast cancer, but also upregulates molecules associated with BLBC [38] . Knockdown of Dub3 inhibits migration, invasion and cancer stem cell (CSC)-like characteristics in cells by downregulating of Snail.…”

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

“…IL-6 is also identified as a major cytokine secreted by BLBC cells and is essential for the CSC-like characteristic of BLBC [41] . Interestingly, Dub3 activity and expression, at both the mRNA and protein levels, can be induced by IL-6 through the JAK/STAT3 signaling pathway [31,38,39] . Consistent with this, we also found that IL-6 rapidly induces Dub3 expression, exerting a maximum effect at 2hr [38] .…”

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

“…The interaction of Snail with Dub3 is mediated at the N-terminal region of Snail, which holds the SNAG domain and is the most common binding site for E3 [38] . Expression of Dub3 blocked Snail degradation mediated by the E3 ligases Fbxl14 and Fbxw1/β-TRCP1 [38] . Functionally, we found that the expression of Dub3 in breast cancer cell lines not only downregulates markers of luminal type of breast cancer, but also upregulates molecules associated with BLBC [38] .…”

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

“…Using siRNA library screen targeting the 99 known or putative DUBs, we identified Dub3 is a deubiquitinase of Snail. Dub3 stabilizes Snail via deubiqutination, downregulating E-cadherin expression and promoting EMT [37,38] . The interaction of Snail with Dub3 is mediated at the N-terminal region of Snail, which holds the SNAG domain and is the most common binding site for E3 [38] .…”

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

“…Dub3 stabilizes Snail via deubiqutination, downregulating E-cadherin expression and promoting EMT [37,38] . The interaction of Snail with Dub3 is mediated at the N-terminal region of Snail, which holds the SNAG domain and is the most common binding site for E3 [38] . Expression of Dub3 blocked Snail degradation mediated by the E3 ligases Fbxl14 and Fbxw1/β-TRCP1 [38] .…”

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

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The regulation of snail: on the ubiquitin edge

Zhou

2017

Can Cell Microenviron

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Metastasis accounts for a majority of cancer death. One key feature during metastasis is epithelial-mesenchymal transition (EMT), which is regulated by transcription factors such as Snail and Twist. In non-malignant cells, Snail has a short half-life and is degraded via ubiquitination, but its stability is increased in cancer cell. However, the mechanism by which Snail escapes ubiquitination and degradation remains unknown. Recently, we found that Dub3 is a deubiquinase of Snail. Most importantly, we determined that Dub3 responded to extracellular signals such as IL-6, and that the resultant signaling prevented Snail degradation, and promoted cancer growth, invasion, and migration. In this highlight, we present a concise picture of how the transcription factor Snail is regulated by ubiquitination in cancer cells, the role of Dub3 in this process, and its potential use as a treatment target.

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Section: The Deubiquitination Of Snailmentioning

confidence: 99%

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

Section: The Deubiquitination Of Snailmentioning

confidence: 99%

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The regulation of snail: on the ubiquitin edge

Zhou

2017

Can Cell Microenviron

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The deubiquitinating enzyme USP17 regulates c‐Myc levels and controls cell proliferation and glycolysis

et al. 2022

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The c‐Myc oncoprotein is frequently overexpressed in human cancers and is essential for cancer cell proliferation. The dysregulation of ubiquitin‐proteasome‐mediated degradation is one of the contributing factors to the upregulated expression of c‐Myc in human cancers. We herein identified USP17 as a novel deubiquitinating enzyme that regulates c‐Myc levels and controls cell proliferation and glycolysis. The overexpression of USP17 stabilized the c‐Myc protein by promoting its deubiquitination. In contrast, the knockdown of USP17 promoted c‐Myc degradation and reduced c‐Myc levels. The knockdown of USP17 also suppressed cell proliferation and glycolysis. Collectively, the present results reveal a novel role for USP17 in the regulation of c‐Myc stability and suggest its potential as a therapeutic target for cancer treatment.

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Deubiquitylating Enzymes in Cancer and Immunity

Ren,

Yu,

Liu

et al. 2023

Advanced Science

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Deubiquitylating enzymes (DUBs) maintain relative homeostasis of the cellular ubiquitome by removing the post‐translational modification ubiquitin moiety from substrates. Numerous DUBs have been demonstrated specificity for cleaving a certain type of ubiquitin linkage or positions within ubiquitin chains. Moreover, several DUBs perform functions through specific protein–protein interactions in a catalytically independent manner, which further expands the versatility and complexity of DUBs’ functions. Dysregulation of DUBs disrupts the dynamic equilibrium of ubiquitome and causes various diseases, especially cancer and immune disorders. This review summarizes the Janus‐faced roles of DUBs in cancer including proteasomal degradation, DNA repair, apoptosis, and tumor metastasis, as well as in immunity involving innate immune receptor signaling and inflammatory and autoimmune disorders. The prospects and challenges for the clinical development of DUB inhibitors are further discussed. The review provides a comprehensive understanding of the multi‐faced roles of DUBs in cancer and immunity.

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Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation

Cited by 105 publications

References 65 publications

The regulation of snail: on the ubiquitin edge

The regulation of snail: on the ubiquitin edge

The deubiquitinating enzyme USP17 regulates c‐Myc levels and controls cell proliferation and glycolysis

Deubiquitylating Enzymes in Cancer and Immunity

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