The Impact of the Ubiquitin System in the Pathogenesis of Squamous Cell Carcinomas

Gatti, Veronica; Bernassola, Francesca; Talora, Claudio; Melino, Gerry; Peschiaroli, Angelo

doi:10.3390/cancers12061595

Cited by 12 publications

(8 citation statements)

References 204 publications

(262 reference statements)

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“…The ubiquitination pathway is widely involved in the regulation of cell cycle, proliferation, apoptosis, differentiation, damage repair, inflammation, immunity, and almost all other life activities [ 42 ]. Aberrant ubiquitin pathway has been functionally linked to the development and progression of many human diseases, including human tumors [ 43 ]. In lung cancer, it was reported that TRIM59 induced ABHD5 ubiquitination, leading to its proteasome-dependent degradation, whereas ABHD5 deficiency leads to metabolic reprogramming of macrophages and activation of NLRP3 inflammatory microsomes, generating an inflammatory environment for tumor development [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of P4HA1 Is Correlated with Poor Survival and Immune Infiltrates in Lung Adenocarcinoma

Zhou

et al. 2020

BioMed Research International

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Lung adenocarcinoma (LUAD) is a major pathological type of lung cancer. Understanding the mechanism of LUAD at the molecular level is important for a clinical decision. In this study, we use bioinformatic analysis to explore the prognostic value of P4HA1 in lung adenocarcinoma (LUAD) and the relationship with prognosis and tumor-infiltrating immune cells (TIICs). The results showed that the expression of P4HA1 was significantly higher in tumor tissues than in normal tissues for LUAD patients. Upregulated P4HA1 was related to stage and T classification. Kaplan-Meier analysis indicated that upregulation of P4HA1 was significantly related to worse overall survival (OS). Univariate and multivariate Cox analysis indicated P4HA1 remained to be an independent prognostic factor. GSEA showed that several cancer-related and immune-related signaling pathways exhibited prominently differential enrichment in P4HA1-high expression phenotype. In addition, the expression of P4HA1 was significantly correlated with proportion of several TIICs, particularly B cells and CD4+ T cells. In conclusion, our study confirmed that P4HA1 is a promising biomarker of poor prognosis and relates to immune infiltrates in LUAD.

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Section: Discussionmentioning

confidence: 99%

Overexpression of P4HA1 Is Correlated with Poor Survival and Immune Infiltrates in Lung Adenocarcinoma

Zhou

et al. 2020

BioMed Research International

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“…The ubiquitination of proteins is a common post-translational modification in most cell types. Disturbances of ubiquitin-mediated processes often result in tumorigenesis and metastasis, including lung cancer [ 99 – 101 ]. Ubiquitination is part of the mechanism leading to the dissociation of AJs during EMT [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

Application of two-dimensional difference gel electrophoresis to identify protein changes between center, margin, and adjacent non-tumor tissues obtained from non-small-cell lung cancer with adenocarcinoma or squamous cell carcinoma subtype

et al. 2022

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Lung cancer is responsible for the most cancer-related mortality worldwide and the mechanism of its development is poorly understood. Proteomics has become a powerful tool offering vital knowledge related to cancer development. Using a two-dimensional difference gel electrophoresis (2D-DIGE) approach, we sought to compare tissue samples from non-small-cell lung cancer (NSCLC) patients taken from the tumor center and tumor margin. Two subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were compared. Data are available via ProteomeXchange with identifier PXD032736 and PXD032962 for ADC and SCC, respectively. For ADC proteins, 26 significant canonical pathways were identified, including Rho signaling pathways, a semaphorin neuronal repulsive signaling pathway, and epithelial adherens junction signaling. For SCC proteins, nine significant canonical pathways were identified, including hypoxia-inducible factor-1α signaling, thyroid hormone biosynthesis, and phagosome maturation. Proteins differentiating the tumor center and tumor margin were linked to cancer invasion and progression, including cell migration, adhesion and invasion, cytoskeletal structure, protein folding, anaerobic metabolism, tumor angiogenesis, EMC transition, epithelial adherens junctions, and inflammatory responses. In conclusion, we identified several proteins that are important for the better characterization of tumor development and molecular specificity of both lung cancer subtypes. We also identified proteins that may be important as biomarkers and/or targets for anticancer therapy.

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“…The oncogenic role of SKP2 reconciles with its overexpression in various human cancers including ovarian adenocarcinoma, breast cancer, lung cancer, colorectal cancer, prostate cancer, leukaemia and squamous cell carcinoma. 103 , 104 , 105 , 106 Interestingly, deletion of SKP2 has been shown to compensate for anti‐tumour and cell safeguarding deficiency in p53 deleted cancer cells due to elevated p27 levels. Zhao and co‐workers demonstrated this using SKP2 knockout mice and found that loss of p53 and pRB in these mice blocked tumorigenesis due to cell cycle arrest mediated by accumulated p27, suggesting that SKP2 could be a promising target for p53 mutant cancer therapy.…”

Section: Roles Of E3 Ligases In Cancer Hallmarksmentioning

confidence: 99%

The roles of E3 ubiquitin ligases in cancer progression and targeted therapy

Sampson

Wang

Otkur

et al. 2023

Clinical & Translational Med

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Ubiquitination is one of the most important post‐translational modifications which plays a significant role in conserving the homeostasis of cellular proteins. In the ubiquitination process, ubiquitin is conjugated to target protein substrates for degradation, translocation or activation, dysregulation of which is linked to several diseases including various types of cancers. E3 ubiquitin ligases are regarded as the most influential ubiquitin enzyme owing to their ability to select, bind and recruit target substrates for ubiquitination. In particular, E3 ligases are pivotal in the cancer hallmarks pathways where they serve as tumour promoters or suppressors. The specificity of E3 ligases coupled with their implication in cancer hallmarks engendered the development of compounds that specifically target E3 ligases for cancer therapy. In this review, we highlight the role of E3 ligases in cancer hallmarks such as sustained proliferation via cell cycle progression, immune evasion and tumour promoting inflammation, and in the evasion of apoptosis. In addition, we summarise the application and the role of small compounds that target E3 ligases for cancer treatment along with the significance of targeting E3 ligases as potential cancer therapy.

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The Impact of the Ubiquitin System in the Pathogenesis of Squamous Cell Carcinomas

Cited by 12 publications

References 204 publications

Overexpression of P4HA1 Is Correlated with Poor Survival and Immune Infiltrates in Lung Adenocarcinoma

Overexpression of P4HA1 Is Correlated with Poor Survival and Immune Infiltrates in Lung Adenocarcinoma

Application of two-dimensional difference gel electrophoresis to identify protein changes between center, margin, and adjacent non-tumor tissues obtained from non-small-cell lung cancer with adenocarcinoma or squamous cell carcinoma subtype

The roles of E3 ubiquitin ligases in cancer progression and targeted therapy

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