Role of tyrosine phosphorylation in modulating cancer cell metabolism

Taddei, Maria Letizia; Pardella, Elisa; Pranzini, Erica; Raugei, Giovanni; Paoli, Paolo De

doi:10.1016/j.bbcan.2020.188442

Cited by 42 publications

(55 citation statements)

References 186 publications

(249 reference statements)

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“…To validate the protein expression of NOP2, CPTAC analysis showed that the NOP2 had a high expression in primary ccRCC tumor than normal kidney tissues in line with its mRNA expression levels. As protein phosphorylation had been revealed to play vital roles in multiple cancers [37][38][39], we also analyzed the NOP2 phosphoprotein expression and found that it was highly expressed in primary ccRCC tumor than normal tissues with phosphorylation sites at the S58, T191 and S728. In order to identify NOP2-related signaling pathways, GSEA, as a useful tool, had been applied by various researchers [40,41].…”

Section: Discussionmentioning

confidence: 99%

Nucleolar protein NOP2 could serve as a potential prognostic predictor for clear cell renal cell carcinoma

Wang

Liu

et al. 2021

Bioengineered

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As an indispensable part for cancer precision medicine, biomarkers and signatures for predicting cancer prognosis and therapeutic benefits were urgently required. The purpose of this study was to investigate the prognostic roles of NOP2 in renal clear cell carcinoma (ccRCC) for overall survival (OS) and its relationships with immunity. NOP2-related gene expression matrix associated with clinical information was obtained from the Cancer Genome Atlas (TCGA) ccRCC dataset and NOP2-related pathways were identified by gene set enrichment analysis (GSEA). Associations among the NOP2 expression and MSI, TMB, TNB, and immunity were also explored. Both the NOP2 mRNA and protein/phosphoprotein had a higher expression in ccRCC tumor tissues than in normal kidney tissues (both P < 0.001) and elevated NOP2 expression was associated with poor OS (P < 0.001). Logistic regression analysis revealed the NOP2 expression was significantly linked to stage, age, grade, N stage, T stage, and M stage (all P < 0.05). Univariate/multivariate Cox hazard regression analysis results indicated that NOP2 was an independent prognostic factor for OS in ccRCC and GSEA revealed five NOP2-related signaling pathways. Nomogram based on NOP2 and eight clinical characteristic parameters (grade, age, stage, gender, T stage, race, M stage, N stage) was constructed and carefully evaluated. Furthermore, NOP2 gene expression was also found to be significantly related to MSI, TMB, and immunity. Our findings revealed that NOP2 might be a potential prognostic factor for OS in ccRCC and it was significantly associated with immunity, MSI, and TMB.

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Section: Discussionmentioning

confidence: 99%

Nucleolar protein NOP2 could serve as a potential prognostic predictor for clear cell renal cell carcinoma

Wang

Liu

et al. 2021

Bioengineered

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“…4 F ) that contains four phosphorylation sites in the cytoplasmic domains (i.e., 19Y, 87T, 182Y, 276S) as predicted using TOPCONS 31 . Under the assumption that phosphorylation signals are largely relayed via cytoplasmic domains and provided with the prominent roles of tyrosine phosphorylation in modulating cancer cell behaviors 32 , 33 , we focused on AQP3-19Y here and mutated it into 19F using the CRISPR/Cas9 technique with ssODN (single-strand oligo-deoxyribonucleotides) being the homologous recombination template ( Fig. 2 M ).…”

Section: Resultsmentioning

confidence: 99%

Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination

Dai¹,

Cai²,

Wang³

et al. 2022

Int. J. Biol. Sci.

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Cold atmospheric plasma (CAP) is selective against many cancers with little side effect, yet its molecular mechanism remains unclear. Through whole transcriptome sequencing followed by assays in vitro , in vivo and using clinical samples, we propose CAP as a promising onco-therapy targeting cancer stemness via the AQP3/FOXO1 axis. CAP-generated reactive species penetrated cells via AQP3 and suppressed RPS6KA3, a shared kinase of AQP3 and FOXO1. Reduced AQP3-19Y phosphorylation suppressed SCAF11-mediated AQP3-5K K48-ubiquitination that led to sabotaged FOXO1 stability. Inhibited FOXO1 phosphorylation retarded its regulatory activities in maintaining cancer stemness including ALDH1 and IL6. Enhanced anti-cancer efficacy was observed through combining CAP with Atorvastatin in vitro and in vivo . We propose CAP as a 'selective' onco-therapeutic against cancer stemness, with the AQP3/FOXO1 axis being one molecular mechanism. We report SCAF11 as an E3 ubiquitin ligase of both AQP3 and FOXO1, identify AQP3-5K as an AQP3 K48-ubiquitination site, and emphasize the essential role of AQP3-19Y in this process. We reposition Atorvastatin into the onco-therapeutic portfolio by synergizing it with CAP towards enhanced efficacy. We anticipate the efficacy of CAP in targeting malignancies of high stemness alone or as an adjuvant therapy towards the hope of ultimate cancer cure.

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“…Among these pathways, the tyrosine metabolism pathway and the arginine and proline metabolism pathways are significantly related to different types of cancer. The phosphorylation of tyrosine is a ubiquitous posttranslational modification that is important for the metabolic reprogramming of cancer cells [ 26 ]. In addition, studies have revealed that the arginine and proline metabolism pathways are relevant to the proliferation and metastasis of human prostate cancer [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolism-Related Bioinformatics Analysis Reveals That HPRT1 Facilitates the Progression of Oral Squamous Cell Carcinoma In Vitro

Huang

et al. 2022

Journal of Oncology

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Objectives. Many studies have shown that dysregulation of metabolism contributes to oncogenesis. However, the exact roles of metabolism-related genes (MRGs) in oral squamous cell carcinoma (OSCC) remain unclear. Thus, we aimed to identify a prognostic signature related to MRGs in OSCC. Methods. The gene sequencing data of OSCC samples and the MRG set were downloaded from The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB). The Wilcoxon rank-sum test was used to identify differentially expressed MRGs. Then, a prognostic signature was established by multivariate Cox regression analysis. Finally, prognosis-related MRGs were selected and further validated in OSCC tissues and cell lines. Results. A prognostic signature that included 8 MRGs was constructed. Multiple survival analysis revealed that only HPRT1 might be an independent biomarker and indicator of poor overall survival in OSCC patients. The expression of HPRT1 was then found to be upregulated in OSCC tissues and cell lines, and suppression of HPRT1 gene expression by siRNA inhibited the proliferation, migration, and invasion of OSCC cells in vitro. Conclusions. MRGs play an important role in the development of OSCC. Furthermore, HPRT1 might be an independent biomarker of OSCC and enhance OSCC proliferation, migration, and invasion in vitro; these results emphasize the potential utility of HPRT1 in OSCC therapy.

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Role of tyrosine phosphorylation in modulating cancer cell metabolism

Cited by 42 publications

References 186 publications

Nucleolar protein NOP2 could serve as a potential prognostic predictor for clear cell renal cell carcinoma

Nucleolar protein NOP2 could serve as a potential prognostic predictor for clear cell renal cell carcinoma

Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination

Metabolism-Related Bioinformatics Analysis Reveals That HPRT1 Facilitates the Progression of Oral Squamous Cell Carcinoma In Vitro

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