USP7 promotes non‐small‐cell lung cancer cell glycolysis and survival by stabilizing and activating c‐Abl

He, Yuanming; Jiang, Shuoyi; Zhong, Yueya; Wang, Xiaoge; Cui, Yaoli; Liang, Jingpei; Sun, Yuening; Zhu, Zhigang; Huang, Zhenqian; Mao, Xinliang

doi:10.1002/ctm2.1509

Cited by 7 publications

(1 citation statement)

References 41 publications

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“…USP7 is a member of the ubiquitin-specific protease family and can scavenge the ubiquitin modification of the substrate, thereby protecting the substrate from proteolysis [ 42 , 68 ]. Previous studies have shown that USP7 plays different roles in the development of cancer [ 69 ]. A recent study showed that high USP7 expression was associated with poor survival and later tumor stage in GBM [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis

Li,

Zhang,

Feng

et al. 2024

J Exp Clin Cancer Res

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Background Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. It is an aggressive tumor characterized by rapid proliferation, diffuse tumor morphology, and poor prognosis. Unfortunately, current treatments, such as surgery, radiotherapy, and chemotherapy, are unable to achieve good outcomes. Therefore, there is an urgent need to explore new treatment targets. A detailed mechanistic exploration of the role of the nuclear pore transporter KPNB1 in GBM is lacking. This study demonstrated that KPNB1 regulated GBM progression through a transcription factor YBX1 to promote the expression of post-protrusion membrane protein NLGN3. This regulation was mediated by the deubiquitinating enzyme USP7. Methods A tissue microarray was used to measure the expression of KPNB1 and USP7 in glioma tissues. The effects of KPNB1 knockdown on the tumorigenic properties of glioma cells were characterized by colony formation assays, Transwell migration assay, EdU proliferation assays, CCK-8 viability assays, and apoptosis analysis using flow cytometry. Transcriptome sequencing identified NLGN3 as a downstream molecule that is regulated by KPNB1. Mass spectrometry and immunoprecipitation were performed to analyze the potential interaction between KPNB1 and YBX1. Moreover, the nuclear translocation of YBX1 was determined with nuclear-cytoplasmic fractionation and immunofluorescence staining, and chromatin immunoprecipitation assays were conducted to study DNA binding with YBX1. Ubiquitination assays were performed to determine the effects of USP7 on KPNB1 stability. The intracranial orthotopic tumor model was used to detect the efficacy in vivo. Results In this study, we found that the nuclear receptor KPNB1 was highly expressed in GBM and could mediate the nuclear translocation of macromolecules to promote GBM progression. Knockdown of KPNB1 inhibited the progression of GBM, both in vitro and in vivo. In addition, we found that KPNB1 could regulate the downstream expression of Neuroligin-3 (NLGN3) by mediating the nuclear import of transcription factor YBX1, which could bind to the NLGN3 promoter. NLGN3 was necessary and sufficient to promote glioma cell growth. Furthermore, we found that deubiquitinase USP7 played a critical role in stabilizing KPNB1 through deubiquitination. Knockdown of USP7 expression or inhibition of its activity could effectively impair GBM progression. In vivo experiments also demonstrated the promoting effects of USP7, KPNB1, and NLGN3 on GBM progression. Overall, our results suggested that KPNB1 stability was enhanced by USP7-mediated deubiquitination, and the overexpression of KPNB1 could promote GBM progression via the nuclear translocation of YBX1 and the subsequent increase in NLGN3 expression. Conclusion This study identified a novel and targetable USP7/KPNB1/YBX1/NLGN3 signaling axis in GBM cells.

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Section: Discussionmentioning

confidence: 99%

Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis

Li,

Zhang,

Feng

et al. 2024

J Exp Clin Cancer Res

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Deubiquitination of Abelson tyrosine kinase: A novel regulatory mechanism targeting non‐small cell lung cancer glycolysis

Yu,

Jiang,

Shan

2024

Clinical and Translational Dis

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In this commentary, we briefly introduce the importance of metabolic reprogramming in non‐small celllung cancer (NSCLC) and the role of aberrant glycolysis processes intumorigenesis and metastasis. We further summarize the regulation of deubiquitylation modification on glycolysis‐related kinases in this system. Andwe discusse the major discovery the research by He Yuanming et al. published in Clinical and Translational Medicine.Their study demonstrates targeting the USP7‐c‐Abl‐HK2 axis represents a promising therapeutic strategt for NSCLC.

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Deubiquitinases as novel therapeutic targets for diseases

Xian,

Ye,

Tang

et al. 2024

MedComm

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Deubiquitinating enzymes (DUBs) regulate substrate ubiquitination by removing ubiquitin or cleaving within ubiquitin chains, thereby maintaining cellular homeostasis. Approximately 100 DUBs in humans counteract E3 ubiquitin ligases, finely balancing ubiquitination and deubiquitination processes to maintain cellular proteostasis and respond to various stimuli and stresses. Given their role in modulating ubiquitination levels of various substrates, DUBs are increasingly linked to human health and disease. Here, we review the DUB family, highlighting their distinctive structural characteristics and chain‐type specificities. We show that DUB family members regulate key signaling pathways, such as NF‐κB, PI3K/Akt/mTOR, and MAPK, and play crucial roles in tumorigenesis and other diseases (neurodegenerative disorders, cardiovascular diseases, inflammatory disorders, and developmental diseases), making them promising therapeutic targets Our review also discusses the challenges in developing DUB inhibitors and underscores the critical role of the DUBs in cellular signaling and cancer. This comprehensive analysis enhances our understanding of the complex biological functions of the DUBs and underscores their therapeutic potential.

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USP7 promotes non‐small‐cell lung cancer cell glycolysis and survival by stabilizing and activating c‐Abl

Cited by 7 publications

References 41 publications

Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis

Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis

Deubiquitination of Abelson tyrosine kinase: A novel regulatory mechanism targeting non‐small cell lung cancer glycolysis

Deubiquitinases as novel therapeutic targets for diseases

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