Role of ribosomal protein mutations in tumor development (Review)

Goudarzi, Kaveh M.; Lindström, Mikael S.

doi:10.3892/ijo.2016.3387

Cited by 157 publications

(121 citation statements)

References 164 publications

(205 reference statements)

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“…These proteins are responsible for coupling bone resorption with bone formation through the SMAD family of signal transduction proteins. The biogenesis of ribosomes is a highly complex and energy‐consuming process that is initiated in the nucleolus (Goudarzi & Lindstrom, 2016), and cytoplasmic ribosomal proteins are upregulated by RANKL‐induced differentiation of osteoclasts. The pathway analysis showed a significant increase in ribosomal proteins (Figure S5A).…”

Section: Resultsmentioning

confidence: 99%

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

et al. 2018

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SummaryExosomes are secreted into the blood by various types of cells. These extracellular vesicles are involved in the contribution of exosomal proteins to osteoblastic or osteoclastic regulatory networks during the failure of bone remodeling, which results in age‐related bone loss. However, the molecular changes in serum‐derived exosomes (SDEs) from aged patients with low bone density and their functions in bone remodeling remain to be fully elucidated. We present a quantitative proteomics analysis of exosomes purified from the serum of the elderly patients with osteoporosis/osteopenia and normal volunteers; these data are available via Proteome Xchange with the identifier PXD006463. Overall, 1,371 proteins were identified with an overlap of 1,160 Gene IDs among the ExoCarta proteins. Bioinformatics analysis and in vitro studies suggested that protein changes in SDEs of osteoporosis patients are not only involved in suppressing the integrin‐mediated mechanosensation and activation of osteoblastic cells, but also trigger the differentiation and resorption of osteoclasts. In contrast, the main changes in SDEs of osteopenia patients facilitated both activation of osteoclasts and formation of new bone mass, which could result in a compensatory elevation in bone remodeling. While the SDEs from aged normal volunteers might play a protective role in bone health through facilitating adhesion of bone cells and suppressing aging‐associated oxidative stress. This information will be helpful in elucidating the pathophysiological functions of SDEs and aid in the development of senile osteoporosis diagnostics and therapeutics.

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Section: Resultsmentioning

confidence: 99%

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

et al. 2018

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“…The abnormality of ribosomal proteins (RPs) are usually associated with increased risk of cancer. 43 In the present study, we quantified 160 RPs in total (Table S-1). As indicated in Figure 6A, the SCAD method rendered the highest iBAQ values of RPs.…”

Section: Resultsmentioning

confidence: 99%

Surfactant and Chaotropic Agent Assisted Sequential Extraction/On-Pellet Digestion (SCAD) for Enhanced Proteomics

Liu

2018

J. Proteome Res.

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As a popular sample preparation approach, filter-aided sample preparation (FASP) has been widely used in proteomic analysis. However, several limitations have been noted, including sample loss during filtration, repetitive centrifugation steps, and the possibility of breakage of filtration membrane. Extraction bias among different sample preparation strategies presents another challenge. To overcome these limitations and address remaining challenges, we developed a novel surfactant and chaotropic agent assisted sequential extraction/on-pellet digestion (SCAD) protocol. The new strategy resulted in higher protein yield and improved peptide recovery and protein coverage compared to two conventional sample preparation methods (FASP and urea). In combination of three strategies, more than 10,000 distinct protein groups were identified with 1% FDR from MDA-MB-231 cells without any prefractionation. This in-depth proteome analysis was accomplished by optimization of protein extraction, enzymatic digestion, LC gradient, and peptide sequencing method. Ingenuity Pathways Analysis (IPA) of proteins exclusively identified in SCAD revealed several crucial signaling pathways that regulate breast cancer progression. SCAD also enabled an unbiased extraction of different categories of proteins (membrane, intracellular, nuclear) associated with tumorigenesis, which integrates the advantages of FASP and urea extraction. This novel strategy expedites comprehensive protein identification, which is applicable for biomarker discovery in various types of cancers.

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“…1b). RPL5 may regulate the MDM2–TP53 axis 20 but was mutated infrequently and is of unknown biological relevance in GCTs. KIT mutations were not observed in our cohort despite sufficient genomic power to detect mutations ( KIT hotspot loci mean coverage: 316×; range: 89–800×), although meta-analysis of our cohort with a separate TGCT WES set 5 confirms KIT as significantly mutated (Extended Data Fig.…”

mentioning

confidence: 99%

Genomic evolution and chemoresistance in germ-cell tumours

Taylor-Weiner

Zack

O’Donnell

et al. 2016

Nature

149

168

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Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes1,2. GCTs are histologically heterogeneous and distinctly curable with chemotherapy3. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs4–6, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types. These tumours also acquire KRAS mutations during the development from precursor to primary disease, and primary testicular GCTs (TGCTs) are uniformly wild type for TP53. In addition, by functional measurement of apoptotic signalling (BH3 profiling) of fresh tumour and adjacent tissue7, we find that primary TGCTs have high mitochondrial priming that facilitates chemotherapy-induced apoptosis. Finally, by phylogenetic analysis of serial TGCTs that emerge with chemotherapy resistance, we show how TGCTs gain additional reciprocal loss of heterozygosity and that this is associated with loss of pluripotency markers (NANOG and POU5F1)8,9 in chemoresistant teratomas or transformed carcinomas. Our results demonstrate the distinct genomic features underlying the origins of this disease and associated with the chemosensitivity phenotype, as well as the rare progression to chemoresistance. These results identify the convergence of cancer genomics, mitochondrial priming and GCT evolution, and may provide insights into chemosensitivity and resistance in other cancers.

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Role of ribosomal protein mutations in tumor development (Review)

Cited by 157 publications

References 164 publications

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

Surfactant and Chaotropic Agent Assisted Sequential Extraction/On-Pellet Digestion (SCAD) for Enhanced Proteomics

Genomic evolution and chemoresistance in germ-cell tumours

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