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Descriptive Proteom...
Descriptive Proteome Analysis to Investigate Context-Dependent Treatment Responses to OXPHOS Inhibition in Colon Carcinoma Cells Grown as Monolayer and Multicellular Tumor Spheroids
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- Steinmetz, Julia (author)
- Karolinska Inst, Div Rheumatol, Dept Med, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
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- Senkowski, Wojciech (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Lengqvist, Johan (author)
- Karolinska Inst, Dept Oncol Pathol, SE-17177 Stockholm, Sweden.
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- Rubin, Jenny (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Ossipova, Elena (author)
- Karolinska Inst, Div Rheumatol, Dept Med, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
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- Herman, Stephanie (author)
- Uppsala universitet,Klinisk kemi
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- Larsson, Rolf (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Jakobsson, Per-Johan (author)
- Karolinska Institutet
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- Fryknäs, Mårten (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Kultima, Kim (author)
- Uppsala universitet,Klinisk kemi
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Karolinska Inst, Div Rheumatol, Dept Med, SE-17176 Stockholm, Sweden;Karolinska Univ Hosp, SE-17176 Stockholm, Sweden. Cancerfarmakologi och beräkningsmedicin (creator_code:org_t)
- 2020-07-06
- 2020
- English.
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In: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:28, s. 17242-17254
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Abstract
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- We have previously identified selective upregulation of the mevalonate pathway genes upon inhibition of oxidative phosphorylation (OXPHOS) in quiescent cancer cells. Using mass spectrometry-based proteomics, we here investigated whether these responses are corroborated on the protein level and whether proteomics could yield unique insights into context-dependent biology. HCT116 colon carcinoma cells were cultured as monolayer cultures, proliferative multicellular tumor spheroids (P-MCTS), or quiescent (Q:MCTS) multicellular tumor spheroids and exposed to OXPHOS inhibitors: nitazoxanide, FCCP, oligomycin, and salinomycin or the HMG-CoA-reductase inhibitor simvastatin at two different doses for 6 and 24 h. Samples were processed using an in-depth bottom-up proteomics workflow resulting in a total of 9286 identified protein groups. Gene set enrichment analysis showed profound differences between the three cell systems and confirmed differential enrichment of hypoxia, OXPHOS, and cell cycle progression-related protein responses in P-MCTS and QMCTS. Treatment experiments showed that the observed drug-induced alterations in gene expression of metabolically challenged cells are not translated directly to the protein level, but the results reaffirmed OXPHOS as a selective vulnerability of quiescent cancer cells. This work provides rationale for the use of deep proteome profiling to identify context-dependent treatment responses and encourages further studies investigating metabolic processes that could be co-targeted together with OXPHOS to eradicate quiescent cancer cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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ACS Omega
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- By the author/editor
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Steinmetz, Julia
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Senkowski, Wojci ...
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Lengqvist, Johan
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Rubin, Jenny
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Ossipova, Elena
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Herman, Stephani ...
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Larsson, Rolf
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Jakobsson, Per-J ...
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Fryknäs, Mårten
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Kultima, Kim
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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ACS Omega
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Uppsala University
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Karolinska Institutet