Cancer stem cells don’t waste their time cleaning—low proteasome activity, a marker for cancer stem cell function

Lenos, Kristiaan; Vermeulen, Louis

doi:10.21037/atm.2016.11.81

Cited by 17 publications

(9 citation statements)

References 85 publications

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“…Activity of the 26S proteasome, a protease complex with regulatory functions in cell cycle, DNA repair, and cell survival, is another CSC marker (131, [174][175][176][177]. In this regard, low 26S proteasome activity correlated with high self-renewal capacity and high tumorigenicity in HNSCC cell lines (178).…”

Section: Csc As Biomarkermentioning

confidence: 99%

The Role of Cancer Stem Cells in Radiation Resistance

et al. 2020

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Cancer stem cells (CSC) are a distinct subpopulation within a tumor. They are able to self-renew and differentiate and possess a high capability to repair DNA damage, exhibit low levels of reactive oxygen species (ROS), and proliferate slowly. These features render CSC resistant to various therapies, including radiation therapy (RT). Eradication of all CSC is a requirement for an effective antineoplastic treatment and is therefore of utmost importance for the patient. This makes CSC the prime targets for any therapeutic approach. Albeit clinical data is still scarce, experimental data and first clinical trials give hope that CSC-targeted treatment has the potential to improve antineoplastic therapies, especially for tumors that are known to be treatment resistant, such as glioblastoma. In this review, we will discuss CSC in the context of RT, describe known mechanisms of resistance, examine the possibilities of CSC as biomarkers, and discuss possible new treatment approaches.

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Section: Csc As Biomarkermentioning

confidence: 99%

The Role of Cancer Stem Cells in Radiation Resistance

et al. 2020

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“…Importantly, Wnt signaling has also been found to be essential for the propagation of cancer stem cells [28]. In conjunction, data show that proteasome complex components were also downregulated in MDA-R cells; low proteasome activity is known to be a potential functional marker for CSC and treatment resistance [29].…”

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis of Breast Cancer Resistance to the Anticancer Drug RH1 Reveals the Importance of Cancer Stem Cells

Kučiauskas

Dreižė

Ger

et al. 2019

Cancers

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Antitumor drug resistance remains a major challenge in cancer chemotherapy. Here we investigated the mechanism of acquired resistance to a novel anticancer agent RH1 designed to be activated in cancer cells by the NQO1 enzyme. Data show that in some cancer cells RH1 may act in an NQO1-independent way. Differential proteomic analysis of breast cancer cells with acquired resistance to RH1 revealed changes in cell energy, amino acid metabolism and G2/M cell cycle transition regulation. Analysis of phosphoproteomics and protein kinase activity by multiplexed kinase inhibitor beads showed an increase in the activity of protein kinases involved in the cell cycle and stemness regulation and downregulation of proapoptotic kinases such as JNK in RH1-resistant cells. Suppression of JNK leads to the increase of cancer cell resistance to RH1. Moreover, resistant cells have enhanced expression of stem cell factor (SCF) and stem cell markers. Inhibition of SCF receptor c-KIT resulted in the attenuation of cancer stem cell enrichment and decreased amounts of tumor-initiating cells. RH1-resistant cells also acquire resistance to conventional therapeutics while remaining susceptible to c-KIT-targeted therapy. Data show that RH1 can be useful to treat cancers in the NQO1-independent way, and targeting of the cancer stem cells might be an effective approach for combating resistance to RH1 therapy.

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“…28 Tumour cells with low proteasome activity exhibited CSC-like properties and resistance to tumour therapies in various human tumour cells. 50 Spheroid cells were CSC-enriched cells 14,51 exhibiting lower chymotrypsinlike-proteasome activity than adherent cells. 52,53 In this study, time-lapse imaging revealed that the ZsG + cells had self-renewal and differentiation capacity through symmetric and asymmetric divisions.…”

Section: Discussionmentioning

confidence: 99%

Visualizing the cancer stem‐like properties of canine tumour cells with low proteasome activity

Koangyong

Hosoya

Murase

et al. 2021

Vet Comparative Oncology

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Cancer stem-like cells (CSCs) cause treatment failure in various tumours; however, establishing CSC-targeted therapies has been hampered by difficulties in the identification and isolation of this small sub-population of cells. Recent studies have revealed that tumour cells with low proteasome activity display a CSC phenotype that can be utilized to image CSCs in canines. This study visualizes and reveals the CSC-like properties of tumour cells with low proteasome activity in HMPOS (osteosarcoma) and MegTCC (transitional cell carcinoma), which are canine cell lines. The parent cells were genetically engineered to express ZsGreen1, a fluorescent protein connected to the carboxyl-terminal degron of canine ornithine decarboxylase that accumulates with low proteasome activity (ZsG + cells). ZsG + cells were imaged and the mode of action of this system was confirmed using a proteasome inhibitor (MG-132), which increased the ZsGreen1 fluorescence intensity. The CSC-like properties of ZsG + cells were evaluated on the basis of cell divisions, cell cycle, the expression of CSC markers and tumourigenicity. ZsG + cells underwent asymmetric divisions and had a low percentage of G0/G1 phase cells; moreover, ZsG + cells expressed CSC markers such as CD133 and showed a large tumourigenic capability. In histopathological analysis, ZsG + cells were widely distributed in the tumour samples derived from ZsG + cells and in the proliferative regions of the tumours. The results of this study indicate that visualized canine tumour cells with low proteasome activity have a CSC-like phenotype and that this visualization system can be utilized to identify and isolate canine CSCs.

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Cancer stem cells don’t waste their time cleaning—low proteasome activity, a marker for cancer stem cell function

Cited by 17 publications

References 85 publications

The Role of Cancer Stem Cells in Radiation Resistance

The Role of Cancer Stem Cells in Radiation Resistance

Proteomic Analysis of Breast Cancer Resistance to the Anticancer Drug RH1 Reveals the Importance of Cancer Stem Cells

Visualizing the cancer stem‐like properties of canine tumour cells with low proteasome activity

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