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While autophagy is thought to be an essential process in some cancer cells, it is unknown if or how such cancer cells can circumvent autophagy inhibition. To address this, we developed a CRISPR/Cas9 assay with dynamic live-cell imaging to measure acute effects of knockout (KO) of autophagy genes compared to known essential and non-essential genes. In some cancer cells, autophagy is as essential for cancer cell growth as mRNA transcription or translation or DNA replication. However, even these highly autophagy-dependent cancer cells evolve to circumvent loss of autophagy by upregulating NRF2, which is necessary and sufficient for autophagy-dependent cells to circumvent ATG7 KO and maintain protein homeostasis. Importantly, however, this adaptation increases susceptibly to proteasome inhibitors. These studies identify a common mechanism of acquired resistance to autophagy inhibition and show that selection to avoid tumor cell dependency on autophagy creates new, potentially actionable cancer cell susceptibilities.
Pubmed ID: 31378590
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This monoclonal targets Atg5 (D5G3) Rabbit mAb
View all literature mentionsThis polyclonal targets STX17 antibody produced in rabbit
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View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets p62/SQSTM1
View all literature mentionsThis monoclonal targets Atg7 (D12B11) Rabbit mAb
View all literature mentionsThis unknown targets Human Atg12
View all literature mentionsThis monoclonal targets Nrf2 antibody [EP1808Y] - Carboxyterminal end
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1650 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SJSA-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H292 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions