Proteasome expression and activity in cancer and cancer stem cells

Voutsadakis, Ioannis A.

doi:10.1177/1010428317692248

Cited by 64 publications

(55 citation statements)

References 126 publications

(179 reference statements)

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“…These insights into complex biogenesis could prove valuable, for example, in the design of future therapeutic strategies aiming to counteract elevated proteasome expression and activity that has been associated with cancer pathobiology (Voutsadakis, ). This is exemplified by current attempts to target proteasomal activity via the chaperone POMP (Goldberg et al , ; Fig C).…”

Section: Discussionmentioning

confidence: 99%

Complex‐centric proteome profiling by SEC ‐ SWATH ‐ MS

Heusel

Bludau

Rosenberger

et al. 2019

Molecular Systems Biology

117

114

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Proteins are major effectors and regulators of biological processes that can elicit multiple functions depending on their interaction with other proteins. The organization of proteins into macromolecular complexes and their quantitative distribution across these complexes is, therefore, of great biological and clinical significance. In this paper, we describe an integrated experimental and computational technique to quantify hundreds of protein complexes in a single operation. The method consists of size exclusion chromatography (SEC) to fractionate native protein complexes, SWATH/DIA mass spectrometry to precisely quantify the proteins in each SEC fraction, and the computational framework CCprofiler to detect and quantify protein complexes by error‐controlled, complex‐centric analysis using prior information from generic protein interaction maps. Our analysis of the HEK293 cell line proteome delineates 462 complexes composed of 2,127 protein subunits. The technique identifies novel sub‐complexes and assembly intermediates of central regulatory complexes while assessing the quantitative subunit distribution across them. We make the toolset CCprofiler freely accessible and provide a web platform, SECexplorer, for custom exploration of the HEK293 proteome modularity.

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Section: Discussionmentioning

confidence: 99%

Complex‐centric proteome profiling by SEC ‐ SWATH ‐ MS

Heusel

Bludau

Rosenberger

et al. 2019

Molecular Systems Biology

117

114

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“…Homeostatic proteasome activity plays a critical role in regulating the physiological activities of cancer cells and contributes to CSC initiation and development. 47,48 During experiments, we were aware that the ODC-degron system worked well to show CSC properties in some cells such as colon cancer cell lines HCT116 and DLD1 32 and pancreatic cancer cell line Panc-1, 31 but did not work in other cancer cell types. Therefore, it is assumed that the success of the ODCdegron system may depend on the degree to which LPA in the cell affects CSC properties.…”

Section: Discussionmentioning

confidence: 99%

“…SW480 cells were divided into three groups, control group, E-cad-Fc(+) group, and epithelial growth factor (EGF) + transforming growth factor (TGF)β1(+) group. A, Time course study of cell morphology (24,48, and 72 h). Cells were cultured on normal tissue culture plate (left), cultured on a non-treated plate coated with E-cad-Fc matrix (middle), or cultured on normal tissue culture plate with medium supplemented by EGF and TGF-β1 (right).…”

Section: Proteasome Activity Assaymentioning

confidence: 99%

E‐cadherin‐Fc chimera protein matrix enhances cancer stem‐like properties and induces mesenchymal features in colon cancer cells

Qian

Yokoyama

et al. 2019

Cancer Science

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Cancer stem cells (CSC) are a subpopulation of tumor cells with properties of high tumorigenicity and drug resistance, which lead to recurrence and poor prognosis. Although a better understanding of CSC is essential for developing cancer therapies, scarcity of the CSC population has hindered such analyses. The aim of the present study was to elucidate whether the E‐cadherin‐Fc chimera protein (E‐cad‐Fc) enhances cancer stem‐like properties because studies show that soluble E‐cadherin stimulates human epithelial growth factor receptor (EGFR) and downstream signaling pathways that are reported to play a crucial role in CSC. For this purpose, we used ornithine decarboxylase (ODC)‐degron–transduced (Degron(+)) KM12SM cells as a CSC model that retains relatively low CSC properties. Compared to cultures without E‐cad‐Fc treatment, we found that E‐cad‐Fc treatment further suppressed proteasome activity and largely enhanced cancer stem‐like properties of ODC‐degron–transduced KM12SM cells. These results include increased expression of stem cell markers Lgr5, Bmi‐1, SOX9, CD44, and CD44v9, aldehyde dehydrogenase (ALDH), and enhancement of robust spheroid formation, and chemoresistance to 5‐fluorouracil (5‐FU) and oxaliplatin (L‐OHP). These effects could be attributed to activation of the EGFR pathway as identified by extensive phosphorylation of EGFR, ERK, PI3K, AKT, and mTOR. In SW480 cells, E‐cad‐Fc matrix induced some CSC markers such as CD44v9 and ALDH. We also found that E‐cad‐Fc matrix showed high efficiency of inducing mesenchymal changes in colon cancer cells. Our data suggest that the E‐cad‐Fc matrix may enhance CSC properties such as enhancement of chemoresistance and sphere formation.

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“…Tumor cells present increased expression of many components of the ubiquitin-proteasome system that is related to the increased proteasome activity observed in those cells 28,29 . On the other hand, proteasome activity is decreased in cancer stem cells (CSCs), probably due to the low metabolic activity of CSCs 30 . As already described, low proteasome activity predisposes tumor-initiating cells to form spheres in osteosarcoma, increasing tumorigenesis.…”

Section: Consequences Of Proteasome Activationmentioning

confidence: 99%

Activation of the ubiquitin-proteasome system: implications for neurodegeneration, aging, and tumorigenesis

Demasi¹

2017

J Neurol Neuromedicine

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Since the discovery of the proteasome (1986), many years passed before researchers explored the benefits of its activation. However, its inhibition, which was first observed in the beginning of the 1990s, gained wide acceptance because of its anti-tumor effect, as proteasome inhibition induces apoptosis. Currently, a proteasome inhibitor is utilized as a clinical tool. However, proteasome activation has been shown to either extend the life span of many cellular and animal models or prevent the accumulation of protein aggregates. Later effect might have an important contribution to neurodegenerative diseases with the hallmark of protein aggregation and the impairment of the proteasome. This short review presents prominent data on proteasome activation, focusing on the 20S catalytic proteasome particle. In addition, the benefits and consequences of proteasome activation in tumor development and progression are discussed.

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Proteasome expression and activity in cancer and cancer stem cells

Cited by 64 publications

References 126 publications

Complex‐centric proteome profiling by SEC ‐ SWATH ‐ MS

Complex‐centric proteome profiling by SEC ‐ SWATH ‐ MS

E‐cadherin‐Fc chimera protein matrix enhances cancer stem‐like properties and induces mesenchymal features in colon cancer cells

Activation of the ubiquitin-proteasome system: implications for neurodegeneration, aging, and tumorigenesis

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