UbcH10 a Major Actor in Cancerogenesis and a Potential Tool for Diagnosis and Therapy

Presta, Ivan; Novellino, Fabiana; Donato, Annalidia; Torre, Domenico La; Palleria, Caterina; Russo, Emilio; Malara, Natalia; Donato, Giuseppe

doi:10.3390/ijms21062041

Cited by 17 publications

(20 citation statements)

References 65 publications

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“…The copyright holder for this preprint this version posted October 6, 2022. ; https://doi.org/10.1101/2022.10.04.510674 doi: bioRxiv preprint identified as a prognostic marker 30 and associated with cancer grade progression 31 and drug resistance 32 . Similar observations were made in colon, ovarian, and bladder cancers, among other types of tumors [33][34][35][36] . Interestingly, UBE2C was associated with BM in a recent publication, where single-cell RNA sequencing of BM from multiple cancers led to the identification of two subgroups, being UBE2C one of the signature genes in the proliferative group 25 .…”

Section: Discussionsupporting

confidence: 83%

UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease

Paisana

Cascão

Custódia

et al. 2022

Preprint

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Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies. Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins. Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases. Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K/mTOR inhibition as a promising anticancer therapy to prevent late-stage metastatic brain cancer.

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Section: Discussionsupporting

confidence: 83%

UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease

Paisana

Cascão

Custódia

et al. 2022

Preprint

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“…The normal progress of this process is related to successful completion of the cell cycle and signal transduction. 28 Our results showed that UBE2C is overexpressed in NSCLC tissues (57.1%) and is rarely expressed in normal tissues (15.6%). We found that UBE2C overexpression was associated with a larger tumor volume, LNM, and later clinical stage, suggesting that it might be involved in the growth and metastasis of NSCLC.…”

Section: Discussionmentioning

confidence: 54%

The Relationship Between UBE2C and AGGF1 Overexpression and Tumor Angiogenesis in Non-Small Cell Lung Cancer

Wang¹,

Shi²,

Tao³

et al. 2021

CMAR

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Background Tumor infiltration and metastasis are the leading causes of death for patients with tumors. Angiogenesis is a prerequisite for tumor growth and metastasis. Angiogenic factor with G patch and FHA domains 1 (AGGF1) is an angiogenic factor, whereas ubiquitin-conjugating enzyme E2C (UBE2C) functions in protein ubiquitination. Microvessel density (MVD) is the most common indicator of tumor microvessels, and vasculogenic mimicry (VM) facilitates blood supply to tumors. This study explored UBE2C and AGGF1 expression in non-small cell lung cancer (NSCLC) and their relationship with angiogenesis and prognosis to identify biological factors that might predict NSCLC infiltration, metastasis, and prognosis. Methods The specimens and clinical pathological data of patients with NSCLC confirmed by pathology after surgical resection between January 2013 and December 2015 were collected. UBE2C and AGGF1 expression, as well as microvessel formation and VM in NSCLC, was observed using immunohistochemistry. The relationships between UBE2C, AGGF1, MVD, VM, and clinical pathological parameters and their relationships with overall survival (OS) and disease-free survival (DFS) were analyzed. Results UBE2C and AGGF1 levels in NSCLC tissues were significantly higher than those in corresponding normal tissues (57.1% vs 15.6 and 59.7% vs 25.3%, respectively; P < 0.05). UBE2C, AGGF1, MVD, and VM were positively correlated with each other ( P < 0.05) and were all related to tumor size, lymph node metastasis, and tumor-node-metastasis stage ( P < 0.05). Kaplan–Meier analysis showed that patient OS and DFS in the UBE2C, AGGF1, VM-positive, and high-MVD groups were reduced (all P < 0.001). Univariate and multivariate analyses showed that UBE2C, AGGF1, VM, and MVD were independent risk factors for NSCLC prognosis. Conclusion UBE2C and AGGF1 overexpression is associated with angiogenesis and poor prognosis and may be important for predicting NSCLC invasion, metastasis, and prognosis.

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“…Their contribution to the ubiquitination of the APC/c RING E3 complex and to cell cycle progression has been extensively studied in breast cancer [ 52 ]. Both UBE2S and UBE2C have been proposed as therapeutic targets in various cancers including EOC [ 52 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

Ubiquitin Proteasome Pathway Transcriptome in Epithelial Ovarian Cancer

Vriend

Nachtigal

2021

Cancers

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In this article, we reviewed the transcription of genes coding for components of the ubiquitin proteasome pathway in publicly available datasets of epithelial ovarian cancer (EOC). KEGG analysis was used to identify the major pathways distinguishing EOC of low malignant potential (LMP) from invasive high-grade serous ovarian carcinomas (HGSOC), and to identify the components of the ubiquitin proteasome system that contributed to these pathways. We identified elevated transcription of several genes encoding ubiquitin conjugases associated with HGSOC. Fifty-eight genes coding for ubiquitin ligases and more than 100 genes encoding ubiquitin ligase adaptors that were differentially expressed between LMP and HGSOC were also identified. Many differentially expressed genes encoding E3 ligase adaptors were Cullin Ring Ligase (CRL) adaptors, and 64 of them belonged to the Cullin 4 DCX/DWD family of CRLs. The data suggest that CRLs play a role in HGSOC and that some of these proteins may be novel therapeutic targets. Differential expression of genes encoding deubiquitinases and proteasome subunits was also noted.

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UbcH10 a Major Actor in Cancerogenesis and a Potential Tool for Diagnosis and Therapy

Cited by 17 publications

References 65 publications

UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease

UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease

The Relationship Between UBE2C and AGGF1 Overexpression and Tumor Angiogenesis in Non-Small Cell Lung Cancer

Ubiquitin Proteasome Pathway Transcriptome in Epithelial Ovarian Cancer

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