ArticleThe Journal of biological chemistry2012
Autophagy is a protective mechanism for human melanoma cells under acidic stress.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 181 citations in OpenAlex.
- Pinocembrin, an anticancer dihydroxyflavanone: from chemistry to cellular interactions and synergistic prospects.Cancer cell international · 2026Review
- Autophagy and mitophagy in dermatological disease: a comprehensive review from molecular pathways to therapeutic frontiers.Biology direct · 2025Review
- Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.Journal of experimental & clinical cancer research : CR · 2025Review
- Metabolic stress-mediated cell death and autophagy in human lung cancer cells.The Journal of pharmacology and experimental therapeutics · 2025Article
- Autophagy as a targeted therapeutic approach for skin cancer: Evaluating natural and synthetic molecular interventions.Cancer pathogenesis and therapy · 2024Review
- Review
- Pharmacological Activation of SIRT3 Modulates the Response of Cancer Cells to Acidic pH.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Melanoma biology and treatment: a review of novel regulated cell death-based approaches.Cancer cell international · 2024Review
- Systems Biology and Cytokines Potential Role in Lung Cancer Immunotherapy Targeting Autophagic Axis.Biomedicines · 2023Review
- PIP5K1C phosphoinositide kinase deficiency distinguishes PIKFYVE-dependent cancer cells from non-malignant cells.Autophagy · 2023Article
- Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro.Cancers · 2023Article
- Chronic acidosis rewires cancer cell metabolism through PPARα signaling.International journal of cancer · 2023Article
- AIM-CICs: an automatic identification method for cell-in-cell structures based on convolutional neural network.Journal of molecular cell biology · 2022Article
- A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation.Cell reports · 2022Article
- Identification of distinct slow mode of reversible adaptation of pancreatic ductal adenocarcinoma to the prolonged acidic pH microenvironment.Journal of experimental & clinical cancer research : CR · 2022Article
- miR-7/TGF-Acta pharmaceutica Sinica. B · 2022Article
- Citrullinated glucose-regulated protein 78 is a candidate target for melanoma immunotherapy.Frontiers in immunology · 2022Article
- The role of PI3'-lipid signalling in melanoma initiation, progression and maintenance.Experimental dermatology · 2022Review
- Ion Channels, Transporters, and Sensors Interact with the Acidic Tumor Microenvironment to Modify Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Lactate and Pyruvate Activate Autophagy and Mitophagy that Protect Cells in Toxic Model of Parkinson's Disease.Molecular neurobiology · 2022Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic hypoxia and alterations in oncogenic signaling contribute to switch cancer cell metabolism from oxidative phosphorylation to aerobic glycolysis. A major consequence of up-regulated glycolysis is the increased production of metabolic acids responsible for the presence of acidic areas within solid tumors. Tumor acidosis is an important determinant of tumor progression and tumor pH regulation is being investigated as a therapeutic target. Autophagy is a cellular catabolic pathway leading to lysosomal degradation and recycling of proteins and organelles, currently considered an important survival mechanism in cancer cells under metabolic stress or subjected to chemotherapy. We investigated the response of human melanoma cells cultured in acidic conditions in terms of survival and autophagy regulation. Melanoma cells exposed to acidic culture conditions (7.0 < pH < 6.2) promptly accumulated LC3+ autophagic vesicles. Immunoblot analysis showed a consistent increase of LC3-II in acidic culture conditions as compared with cells at normal pH. Inhibition of lysosomal acidification by bafilomycin A1 further increased LC3-II accumulation, suggesting an active autophagic flux in cells under acidic stress. Acute exposure to acidic stress induced rapid inhibition of the mammalian target of rapamycin signaling pathway detected by decreased phosphorylation of p70S6K and increased phosphorylation of AMP-activated protein kinase, associated with decreased ATP content and reduced glucose and leucine uptake. Inhibition of autophagy by knockdown of the autophagic gene ATG5 consistently reduced melanoma cell survival in low pH conditions. These observations indicate that induction of autophagy may represent an adaptation mechanism for cancer cells exposed to an acidic environment. Our data strengthen the validity of therapeutic strategies targeting tumor pH regulation and autophagy in progressive malignancies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.