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Cells are subjected to oxidative stress during the initiation and progression of tumors, and this imposes selective pressure for cancer cells to adapt mechanisms to tolerate these conditions. Here, we examined the dependency of cancer cells on glutathione (GSH), the most abundant cellular antioxidant. While cancer cell lines displayed a broad range of sensitivities to inhibition of GSH synthesis, the majority were resistant to GSH depletion. To identify cellular pathways required for this resistance, we carried out genetic and pharmacologic screens. Both approaches revealed that inhibition of deubiquitinating enzymes (DUBs) sensitizes cancer cells to GSH depletion. Inhibition of GSH synthesis, in combination with DUB inhibition, led to an accumulation of polyubiquitinated proteins, induction of proteotoxic stress, and cell death. These results indicate that depletion of GSH renders cancer cells dependent on DUB activity to maintain protein homeostasis and cell viability and reveal a potentially exploitable vulnerability for cancer therapy.
Pubmed ID: 30799286 RIS Download
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This monoclonal targets HO-1 (D60G11) Rabbit mAb
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View all literature mentionsCell line NCI-H2228 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1299 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H2030 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line ZR-75-30 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1838 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line NCI-H460 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line HCC1954 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-20 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line ZR-75-30 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line HCC202 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-474 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-436 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC70 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1954 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1569 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThis monoclonal targets USP10 (D7A5) Rabbit mAb
View all literature mentionsThis monoclonal targets UBPY (E-1)
View all literature mentionsThis monoclonal targets HO-1 (D60G11) Rabbit mAb
View all literature mentionsThis monoclonal targets Ubiquitin
View all literature mentionsThis polyclonal targets USP7
View all literature mentionsThis monoclonal targets γ-GCSc
View all literature mentionsCell line NCI-H460 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H2228 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H2030 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1838 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets beta Actin
View all literature mentionsThis monoclonal targets Txn1
View all literature mentionsThis monoclonal targets Glutathione Peroxidase 4 antibody [EPNCIR144]
View all literature mentionsThis monoclonal targets HAUSP (D17C6) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Influenza A Virus HA tag
View all literature mentionsThis monoclonal targets BiP
View all literature mentionsThis monoclonal targets Hsp70
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