Usp8 promotes tumor cell migration through activating the JNK pathway

Zhao, Yunhe; Peng, Dezhen; Liu, Yanyun; Zhang, Qian; Liu, Bin; Deng, Yanran; Ding, Wenhao; Zhou, Zizhang; Liu, Qingxin

doi:10.1038/s41419-022-04749-1

Cited by 11 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By studying genetic interactions between Ter94 and key components of the Hippo pathway, we gained insight into how Ter94 modulates wing size. Because manipulating the Hippo pathway activity throughout the wing would result in deformation, we chose ptc -gal4 to drive transgene expression specifically between vein L3 and vein L4 43 . Compared to the control wing (Fig.…”

Section: Resultsmentioning

confidence: 99%

The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway

Li,

Ding,

Deng

et al. 2024

Commun Biol

Self Cite

View full text Add to dashboard Cite

Insect wing development is a fascinating and intricate process that involves the regulation of wing size through cell proliferation and apoptosis. In this study, we find that Ter94, an AAA-ATPase, is essential for proper wing size dependently on its ATPase activity. Loss of Ter94 enables the suppression of Hippo target genes. When Ter94 is depleted, it results in reduced wing size and increased apoptosis, which can be rescued by inhibiting the Hippo pathway. Biochemical experiments reveal that Ter94 reciprocally binds to Mer, a critical upstream component of the Hippo pathway, and disrupts its interaction with Ex and Kib. This disruption prevents the formation of the Ex-Mer-Kib complex, ultimately leading to the inactivation of the Hippo pathway and promoting proper wing development. Finally, we show that hVCP, the human homolog of Ter94, is able to substitute for Ter94 in modulating Drosophila wing size, underscoring their functional conservation. In conclusion, Ter94 plays a positive role in regulating wing size by interfering with the Ex-Mer-Kib complex, which results in the suppression of the Hippo pathway.

show abstract

Section: Resultsmentioning

confidence: 99%

The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway

Li,

Ding,

Deng

et al. 2024

Commun Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Inhibition of tumor cell metastasis plays a crucial role in the prevention and treatment of malignant tumors. 19 In this study, the effect of 3cb on tumor cell metastasis was investigated by wound scratch and transwell assay, and the results are shown in Fig. 5.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and evaluation of multi-pharmacophore-containing spiropolycyclic harmaline-based hybrids as anticancer agents

Chen

Wang

et al. 2023

New J. Chem.

View full text Add to dashboard Cite

show abstract

“…[44][45][46][47][48] High expression of USP8 is usually associated with the high proliferation and metastasis abilities of tumors. [49] It is reported that USP8 decreases the efficacy of anti-PD-L1/PD-1 immunotherapy via reshaping an inflamed tumor microenvironment (TME). In several murine tumor models, anti-PD-L1/PD-1 immunotherapy combination with USP8 inhibitor significantly increases the infiltration of CD8+ T cells and suppresses tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Targeting USP8 Inhibits O‐GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT

Tang,

Long,

et al. 2023

Advanced Science

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a lethal and aggressive human malignancy. The present study examins the anti‐tumor effects of deubiquitylating enzymes (DUB) inhibitors in HCC. It is found that the inhibitor of ubiquitin specific peptidase 8 (USP8) and DUB‐IN‐3 shows the most effective anti‐cancer responses. Targeting USP8 inhibits the proliferation of HCC and induces cell ferroptosis. In vivo xenograft and metastasis experiments indicate that inhibition of USP8 suppresses tumor growth and lung metastasis. DUB‐IN‐3 treatment or USP8 depletion decrease intracellular cystine levels and glutathione biosynthesis while increasing the accumulation of reactive oxygen species (ROS). Mechanistical studies reveal that USP8 stabilizes O‐GlcNAc transferase (OGT) via inhibiting K48‐specific poly‐ubiquitination process on OGT protein at K117 site, and STE20‐like kinase (SLK)‐mediated S716 phosphorylation of USP8 is required for the interaction with OGT. Most importantly, OGT O‐GlcNAcylates solute carrier family 7, member 11 (SLC7A11) at Ser26 in HCC cells, which is essential for SLC7A11 to import the cystine from the extracellular environment. Collectively, this study demonstrates that pharmacological inhibition or knockout of USP8 can inhibit the progression of HCC and induce ferroptosis via decreasing the stability of OGT, which imposes a great challenge that targeting of USP8 is a potential approach for HCC treatment.

show abstract

Usp8 promotes tumor cell migration through activating the JNK pathway

Cited by 11 publications

References 44 publications

The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway

The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway

Design, synthesis and evaluation of multi-pharmacophore-containing spiropolycyclic harmaline-based hybrids as anticancer agents

Targeting USP8 Inhibits O‐GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT

Contact Info

Product

Resources

About