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USP7 activates Wnt. 21 / 21
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"Our previous and present study showed that USP7 positively regulated Wnt signaling via deubiquitinating β-catenin, enriching possible mechanisms by which USP7 conduces to tumorigenesis [20] ."
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"USP7 enhances Wnt signaling activity by stabilizing the β-catenin protein, which contributes to tumor growth."
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"Studies have found that USP7 inhibitors P5091 and Parthenolide inhibits Wnt signaling and colorectal tumor growth ; specific inhibitor HBX 19818 can selectively reduce the activity of USP7 ; USP7 small-molecule inhibitors P5091 and P22077 can induce tumor cell apoptosis by enhancing intracellular oxidative stress response and endoplasmic reticulum stress response [ 40,188,189,190,191 ] ."
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"Transient targeting of USP7 in APC4 cells immediately after transfection significantly suppressed Wnt transcriptional activity, while such suppression was gradually lost upon colony picking (XREF_SUPPLEMENTARY B)."
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"To prove that the USP7 mediated Wnt activation is p53 independent, we further targeted USP7 in the APC mutated CRC cell line SW480 carrying the p53 mutation."
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"beta-Catenin (Ser33Y) expression significantly rescued the number of colonies formed as well as the Wnt transcriptional activity mediated by USP7 CRISPR mutation in both cells (XREF_FIG H and XREF_SUPPLEMENTARY L), suggesting that the growth defect upon USP7 loss is due to modulation of Wnt signaling."
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"Similar to the WT HEK293T cells, CRISPR targeting of USP7 in HCT116 cells did not suppress Wnt activation (XREF_FIG I)."
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"Targeting USP7 with Small-Molecule Inhibitors Suppresses Wnt Activation in CRCs Carrying CID Deleted APC Mutations."
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"Overall, USP7 overexpression could promote OS cell metastasis by activating the Wnt and beta-catenin signalling pathway by inducing EMT, suggesting that USP7 is a potential therapeutic target for OS."
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"In summary, USP7 inhibition by CRISPR targeting or treatment with two different small molecules consistently suppresses aberrant Wnt activation in CID-loss APC mutant cells."
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"Another group recently proposed, using a small interfering RNA (siRNA) knockdown strategy, that USP7 enhances Wnt signaling through RNF220 dependent beta-catenin deubiquitination, which is inconsistent with our current findings."
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"USP7 also activates Wnt signaling in adenomatous polyposis coli gene ( APC ) - mutated colorectal cancer through beta-catenin deubiquitination ( Novellasdemunt et al. 2017 ) ."
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"Specific inhibitors of USP7 (P5091 and parthenolide) were shown to attenuate Wnt and beta-catenin-induced proliferation and migration and suppress tumor growth in HCT116 xenograft mouse models and are yet to be examined in clinical settings [XREF_BIBR, XREF_BIBR]."
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"Genetic ablation or pharmacological inhibition of USP7 robustly increases Wnt/beta-catenin signaling in multiple cellular systems."
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"By stabilising DDX3X, USP7 increases Wnt/beta‐catenin signalling, which has previously been demonstrated to be strongly correlated with colorectal cancer cell invasiveness."
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"USP7 stabilizes β-catenin through deubiquitination and activates the Wnt signalling pathway, whereas the β-catenin inhibitory domain of APC protects β-catenin from deubiquitination by USP7 (148)."
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"USP7 can activate Wnt signaling through deubiquitinating P-catenin ."
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"USP7, a DUB, promotes migration by activating WNT signaling via EMT/β-catenin in OS ."
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"Knockdown of USP7 in colorectal cancer cell lines with hyperactivated Wnt signaling downregulates the activity of Wnt signaling and expression of Wnt target genes, indicating a potentially novel role [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In colon cancer cells with stimulated Wnt signaling, knockdown of RNF220 or USP7 impairs Wnt signaling and expression of Wnt target genes, suggesting a potentially novel role of RNF220 in Wnt related tumorigenesis."
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"We showed that APC truncations lacking the CID make β-catenin vulnerable to USP7 deubiquitination: depletion of USP7 in APC-mutant CRC cell lines and mouse organoids inhibits WNT and suppresses cell growth."
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