ArticleAutophagy2024
ATF6 supports lysosomal function in tumor cells to enable ER stress-activated macroautophagy and CMA: impact on mutant TP53 expression.
Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Cyclosporine A promotes renal fibrosis through activating endoplasmic reticulum stress by targeting miR-212-5p/ATF6 axis.Journal of translational medicine · 2026Article
- Metabolic adaptation to IMMT deficiency through the ATF6-PPARγ axis is contingent on TP53 mutation status in breast cancer.Cell death & disease · 2026Article
- Article
- Identification and validation of an endoplasmic reticulum stress related model to predict prognosis and tumor microenvironment in neuroblastoma.BMC cancer · 2026Article
- HOXA2 exerts anti-renal fibrosis effects through reducing endoplasmic reticulum stress via the upregulation of SIRT1.Communications biology · 2025Article
- The Dynamic UPR Rheostat Orchestrates Single-Cell Plasticity in Glioblastoma.Journal of molecular neuroscience : MN · 2025Article
- Lysosome stress response and mitochondria injury are the earliest detectable alteration in FSGS.Scientific reports · 2025Article
- Mutant p53 upregulates HDAC6 to resist ER stress and facilitates Ku70 deacetylation, which prevents its degradation and mitigates DNA damage in colon cancer cells.Cell death discovery · 2025Article
- The role of autophagy in fibrosis: Mechanisms, progression and therapeutic potential (Review).International journal of molecular medicine · 2025Review
- Post-Translational Modifications (PTMs) of mutp53 and Epigenetic Changes Induced by mutp53.Biology · 2024Review
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- The Role of ER Stress and the Unfolded Protein Response in Cancer.Cancer genomics & proteomicsReview
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibition of the unfolded protein response (UPR), which usually protects cancer cells from stress, may be exploited to potentiate the cytotoxic effect of drugs inducing ER stress. However, in this study, we found that ER stress and UPR activation by thapsigargin or tunicamycin promoted the lysosomal degradation of mutant (MUT) TP53 and that the inhibition of the UPR sensor ATF6, but not of ERN1/IRE1 or EIF2AK3/PERK, counteracted such an effect. ATF6 activation was indeed required to sustain the function of lysosomes, enabling the execution of chaperone-mediated autophagy (CMA) as well as of macroautophagy, processes involved in the degradation of MUT TP53 in stressed cancer cells. At the molecular level, by pharmacological and genetic approaches, we demonstrated that the inhibition of ATF6 correlated with the activation of MTOR and with TFEB and LAMP1 downregulation in thapsigargin-treated MUT TP53 carrying cells. We hypothesize that the rescue of MUT TP53 expression by ATF6 inhibition, could further activate MTOR and maintain lysosomal dysfunction, further inhibiting MUT TP53 degradation, in a vicious circle. The findings of this study suggest that the presence of MUT TP53, which often exerts oncogenic properties, should be considered before approaching treatments combining ER stressors with ATF6 inhibitors against cancer cells, while it could represent a promising strategy against cancer cells that harbor WT TP53.
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