ArticleCancer immunology, immunotherapy : CII2021
Downregulated ATP6V1B1 expression acidifies the intracellular environment of cancer cells leading to resistance to antibody-dependent cellular cytotoxicity.
Article in Cancer immunology, immunotherapy : CII, 2021. 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, 20 citations in OpenAlex.
- ATP6V0B promotes the tumorigenesis of bladder cancer by activating PAQR4/PI3K/AKT signaling.BMC cancer · 2025Article
- ATP6V1B1 regulates ovarian cancer progression and cisplatin sensitivity through the mTOR/autophagy pathway.Molecular and cellular biochemistry · 2025Article
- V-ATPase in cancer: mechanistic insights and therapeutic potentials.Cell communication and signaling : CCS · 2024Review
- Transcriptome and Metabolome Analyses Reveal High-Altitude Adaptation Mechanism of Epididymis Sperm Maturation in Tibetan Sheep.Animals : an open access journal from MDPI · 2024Article
- Identifying key pathogenic mechanisms and potential intervention targets for recurrence after laryngeal cancer treatment through bioinformatics screening.Translational cancer research · 2024Article
- Antibody dependent cell-mediated cytotoxicity selection pressure induces diverse mechanisms of resistance.Cancer biology & therapy · 2023Article
- Cellular senescence triggers intracellular acidification and lysosomal pH alkalinized via ATP6AP2 attenuation in breast cancer cells.Communications biology · 2023Article
- Deciphering a cell death-associated signature for predicting prognosis and response to immunotherapy in lung squamous cell carcinoma.Respiratory research · 2023Article
- High ATP6V1B1 expression is associated with poor prognosis and platinum‑based chemotherapy resistance in epithelial ovarian cancer.Oncology reports · 2023Article
- The V-ATPases in cancer and cell death.Cancer gene therapy · 2022Review
- X-box binding protein 1 (XBP1): a potential role in chemotherapy response, clinical pathologic features, non-inflamed tumour microenvironment for breast cancer.Bioscience reports · 2022Article
- Prediction of Biochemical Recurrence-Free Survival of Prostate Cancer Patients Leveraging Multiple Gene Expression Profiles in Tumor Microenvironment.Frontiers in oncology · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Among several mechanisms for the resistance of human epidermal growth factor receptor 2-overexpressing (HER2 +) cancer cells to trastuzumab, little is known regarding the mechanism underlying the resistance to trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Cell death due to ADCC is caused by apoptosis of target cells induced by granzymes released from natural killer cells. Because optimal granzyme physiological activity occurs at neutral pH, we assumed that the pH of the intracellular environment influences the cytotoxic effects of granzymes. We established ADCC-resistant cells and compared them with wild-type cells in terms of the expression of intracellular pH-regulating genes. The expression of ATP6V1B1, which encodes a component of vacuolar ATPases, was downregulated in the ADCC-resistant cells. Thus, to functionally characterize ATP6V1B1, we used a CRISPR/Cas9 system to generate ATP6V1B1-knockout SKBR3 and JIMT-1 cells (both HER2 + human breast cancer cell line). The resulting cells exhibited significantly less ADCC than the control SKBR3 and JIMT-1 cells. The intracellular pH of the ATP6V1B1-knockout SKBR3 and JIMT-1 cells was significantly lower than control SKBR3 and JIMT-1cells. An analysis of granzyme dynamics during the ADCC reaction in cancer cells revealed that granzymes degraded intracellularly in the control SKBR3 and JIMT-1 cells and accumulated in ATP6V1B1-knockout cells, but were not cytotoxic. These findings suggest that decreased vacuolar ATPase activity alters the cytoplasmic pH of cancer cells to create an environment that is less suitable for granzyme bioactivity, which adversely affects the induction of apoptosis of cancer cells by NK cells.
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