ArticleThe Journal of biological chemistry2012
Acidosis promotes Bcl-2 family-mediated evasion of apoptosis: involvement of acid-sensing G protein-coupled receptor Gpr65 signaling to Mek/Erk.
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 36 papers.
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Who cites it
36 citing papers in PubMed.
- Review
- Acidosis, Iron Dyshomeostasis and Inflammatory Injury.International journal of molecular sciences · 2026Review
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Review
- Proton Sensing GPCR's: The missing link to Warburg's Oncogenic Legacy?Journal of cancer biology · 2024Article
- Proton-sensing ion channels, GPCRs and calcium signaling regulated by them: implications for cancer.Frontiers in cell and developmental biology · 2024Review
- Article
- Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells.Journal of cellular and molecular medicine · 2023Article
- Physiological relevance of proton-activated GPCRs.Pflugers Archiv : European journal of physiology · 2022Review
- miRNA-7062-5p Promoting Bone Resorption After Bone Metastasis of Colorectal Cancer Through Inhibiting GPR65.Frontiers in cell and developmental biology · 2021Article
- Regulation of autophagy by canonical and non-canonical ER stress responses.Seminars in cancer biology · 2020Review
- Review
- The acidic tumor microenvironment drives a stem-like phenotype in melanoma cells.Journal of molecular medicine (Berlin, Germany) · 2020Article
- [Effect of Fei-Liu-Ping ointment combined with cyclophosphamide on lung cancer cell proliferation and acidic microenvironment].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2020Article
- The impact of tumour pH on cancer progression: strategies for clinical intervention.Exploration of targeted anti-tumor therapy · 2020Review
- Lactate and Lactate Transporters as Key Players in the Maintenance of the Warburg Effect.Advances in experimental medicine and biology · 2020Review
- Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia.Redox biology · 2019Article
- Review
- Chromatin accessibility changes are associated with enhanced growth and liver metastasis capacity of acid-adapted colorectal cancer cells.Cell cycle (Georgetown, Tex.) · 2019Article
- Acid microenvironment promotes cell survival of human bone sarcoma through the activation of cIAP proteins and NF-κB pathway.American journal of cancer research · 2019Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.5) blocks apoptosis induced by multiple cytotoxic metabolic stresses, including deprivation of glucose or glutamine and treatment with dexamethasone. We sought to examine the role of the Bcl-2 family of apoptosis regulators in this process. Interestingly, we found that acidic culture causes elevation of both Bcl-2 and Bcl-xL, while also attenuating glutamine starvation-induced elevation of p53-up-regulated modulator of apoptosis (PUMA) and Bim. We confirmed with knockdown studies that these shifts direct survival decisions during starvation and acidosis. Importantly, the promotion of a high anti- to pro-apoptotic Bcl-2 family member ratio by acidosis renders cells exquisitely sensitive to the Bcl-2/Bcl-xL antagonist ABT-737, suggesting that acidosis causes Bcl-2 family dependence. This dependence appears to be mediated, in part, by the acid-sensing G protein-coupled receptor, GPR65, via a MEK/ERK pathway.
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