Proteomic Profiling Identified Multiple Short-lived Members of the Central Proteome as the Direct Targets of the Addicted Oncogenes in Cancer Cells

Qi, Tonggang; Zhang, Wei; Luan, Yun; Kong, Feng; Xu, Dawei; Cheng, Guanghui; Wang, Yunshan

doi:10.1074/mcp.m113.027813

Cited by 13 publications

(19 citation statements)

References 45 publications

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“…41 19S lid component PSMD11 was among the top down-regulated proteins after PI3K inhibition in lung and pancreatic cancer cells in another proteomic study. 42 Consistent with the association of low cycling and low proteasome activity, normal human embryonic stem cells (hESCs), which, in contrast to CSC counterparts, have a high cycling activity during developmental organogenesis, possess a high proteasome activity. 43 This is an important distinction to emphasize with pathogenic and possible therapeutic implications.…”

Section: Proteasome Activity In Cancer and Cscsmentioning

confidence: 86%

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Proteasome expression and activity in cancer and cancer stem cells

Voutsadakis

2017

Tumour Biol.

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Proteasome is a multi-protein organelle that participates in cellular proteostasis by destroying damaged or short-lived proteins in an organized manner guided by the ubiquitination signal. By being in a central place in the cellular protein complement homeostasis, proteasome is involved in virtually all cell processes including decisions on cell survival or death, cell cycle, and differentiation. These processes are important also in cancer, and thus, the proteasome is an important regulator of carcinogenesis. Cancers include a variety of cells which, according to the cancer stem cell theory, descend from a small percentage of cancer stem cells, alternatively termed tumor-initiating cells. These cells constitute the subsets that have the ability to propagate the whole variety of cancer and repopulate tumors after cytostatic therapies. Proteasome plays a role in cellular processes in cancer stem cells, but it has been found to have a decreased function in them compared to the rest of cancer cells. This article will discuss the transcriptional regulation of proteasome sub-unit proteins in cancer and in particular cancer stem cells and the relationship of the proteasome with the pluripotency that is the defining characteristic of stem cells. Therapeutic opportunities that present from the understanding of the proteasome role will also be discussed.

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Section: Proteasome Activity In Cancer and Cscsmentioning

confidence: 86%

“…41 19S lid component PSMD11 was among the top down-regulated proteins after PI3K inhibition in lung and pancreatic cancer cells in another proteomic study. 42…”

Section: Proteasome Activity In Cancer and Cscsmentioning

confidence: 99%

Proteasome expression and activity in cancer and cancer stem cells

Voutsadakis

2017

Tumour Biol.

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“…PSMD11 was overexpressed in breast cancer tissue, and this may be associated with specific biological processes and pathological types of breast cancer (65). PSMD11 is a short-lived protein, and knockdown of PSMD11 via RNA interference partially resulted in the occurrence of acute apoptosis in pancreatic cancer cells (66). It was identified that high expression of PSMD3 and PSMD11 was associated with poor overall survival in patients with melanoma.…”

Section: Discussionmentioning

confidence: 99%

Identification of key candidate genes involved in melanoma metastasis

Chen

Shi

et al. 2019

Mol Med Report

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Metastasis is the most lethal stage of cancer progression. The present study aimed to investigate the underlying molecular mechanisms of melanoma metastasis using bioinformatics. Using the microarray dataset GSE8401 from the Gene Expression Omnibus database, which included 52 biopsy specimens from patients with melanoma metastasis and 31 biopsy specimens from patients with primary melanoma, differentially expressed genes (DEGs) were identified, subsequent to data preprocessing with the affy package, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed. Mutated genes were analyzed with 80 mutated cases with melanoma from The Cancer Genome Atlas. The overall survival of key candidate DEGs, which were within a filtering of degree >30 criteria in the PPI network and involved three or more KEGG signaling pathways, and genes with a high mutation frequency were delineated. The expression analysis of key candidate DEGs, mutant genes and their associated genes were performed on UALCAN. Of the 1,187 DEGs obtained, 505 were upregulated and 682 were downregulated. ‘Extracellular exosome’ processes, the ‘amoebiasis’ pathway, the ‘ECM-receptor interaction’ pathway and the ‘focal adhesion’ signaling pathway were significantly enriched and identified as important processes or signaling pathways. The overall survival analysis of phosphoinositide-3-kinase regulator subunit 3 ( PIK3R3 ), centromere protein M ( CENPM ), aurora kinase A ( AURKA ), laminin subunit α 1 ( LAMA1 ), proliferating cell nuclear antigen ( PCNA ), adenylate cyclase 1 ( ADCY1 ), BUB1 mitotic checkpoint serine/threonine kinase ( BUB1 ), NDC80 kinetochore complex component ( NDC80 ) and protein kinase C α ( PRKCA ) in DEGs was statistically significant. Mutation gene analysis identified that BRCA1-associated protein 1 ( BAP1 ) had a higher mutation frequency and survival analysis, and its associated genes in the BAP1 -associated PPI network, including ASXL transcriptional regulator 1 ( ASXL1 ), proteasome 26S subunit, non-ATPase 3 ( PSMD3 ), proteasome 26S subunit, non ATPase 11 ( PSMD11 ) and ubiquitin C ( UBC ), were statistically significantly associated with the overall survival of patients with melanoma. The expression levels of PRKCA, BUB1, BAP1 and ASXL1 were significantly different between primary melanoma and metastatic melanoma. Based on the present study, ‘extracellular exosome’ processes, ‘amoebiasis’ pathways, ‘ECM-receptor interaction’ pathways and ‘focal adhesion’ signaling pathways may be important in the formation of metastases from melanoma. Th...

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“…After 4 hr, the expression of PSMD11 all increased to a higher level (about 2.1‐folds for MiaPaCa‐2 and 2.5‐folds for PANC‐1 cells) compared to normal control, indicating that HHT could also not inhibit induction of protein synthesis of PSMD11 in pancreatic cancer cells. For PSMD11 had been demonstrated to be an acute apoptosis inhibitor in our previous studies, these data suggested that selectively induction of protein synthesis of PSMD11 following treatment with protein synthesis inhibitors might be one of the common and important mechanism by which pancreatic cancer cells could avoid quick apoptosis.…”

Section: Resultsmentioning

confidence: 67%

Homoharringtonine could induce quick protein synthesis of PSMD11 through activating MEK1/ERK1/2 signaling pathway in pancreatic cancer cells

Wang

Zhao

Guo³

et al. 2018

J of Cellular Biochemistry

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Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating disease with the 5-year survival rate less than 6%. In this study, we investigated if inhibiting protein synthesis directly with homoharringtonine (HHT) could induce acute apoptosis in pancreatic cancer cells through quick depletion of multiple short-lived critical members of the central proteome, example, PSMD11(26S proteasome non-ATPase regulatory subunit 11). It was shown that although HHT could inhibit proliferation and growth of MiaPaCa-2 and PANC-1 cells in a time- and dose-dependent manner, only part of pancreatic cancer cells could be induced to die through acute apoptosis. Mechanistic studies showed that HHT could induce quick protein synthesis of PSMD11 through activating MEK1/ERK1/2 signaling pathway in pancreatic cancer cells. Inhibiting MEK1/ERK1/2 pathway with sorafenib could improve the cytotoxity of HHT in vitro and in a genetically engineered mouse model of pancreatic cancer. These results suggest that quick induction of PSMD11 or other acute apoptosis inhibitors through activation of the MEK1/ERK1/2 signaling pathway may be one of the important surviving mechanism which can help pancreatic cancer cells avoid acute apoptosis, it may have significant implications for the targeted therapy of pancreatic ductal adenocarcinoma.

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Proteomic Profiling Identified Multiple Short-lived Members of the Central Proteome as the Direct Targets of the Addicted Oncogenes in Cancer Cells

Cited by 13 publications

References 45 publications

Proteasome expression and activity in cancer and cancer stem cells

Proteasome expression and activity in cancer and cancer stem cells

Identification of key candidate genes involved in melanoma metastasis

Homoharringtonine could induce quick protein synthesis of PSMD11 through activating MEK1/ERK1/2 signaling pathway in pancreatic cancer cells

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