ArticleOncotarget2017
Osteoclast proton pump regulator Atp6v1c1 enhances breast cancer growth by activating the mTORC1 pathway and bone metastasis by increasing V-ATPase activity.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- Modeling and targeting the hostile physicochemical niche in bone metastasis: from experimental platforms to niche-directed therapy.Frontiers in cell and developmental biology · 2026Review
- Tear Biomarkers of Topical Sirolimus in Meibomian Gland Dysfunction: A Randomized Trial.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- Integrative single-cell and bulk RNA-seq analysis identifies lactylation-related signature in osteosarcoma.Functional & integrative genomics · 2025Article
- From neuromodulation to bone homeostasis: therapeutic targets of nerve growth factor in skeletal diseases.Frontiers in pharmacology · 2025Review
- Irisin's Dual Role in Malignant Tumors and Its Potential as a Biomarker and Therapeutic Target.Drug design, development and therapy · 2025Review
- Article
- Unveiling biomarker detection in Alzheimer's disease: a computational approach to microarray analysis.3 Biotech · 2024Article
- Article
- High ATP6V1B1 expression is associated with poor prognosis and platinum‑based chemotherapy resistance in epithelial ovarian cancer.Oncology reports · 2023Article
- Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro.Scientific reports · 2023Article
- Identification of a five-gene signature deriving from the vacuolar ATPase (V-ATPase) sub-classifies gliomas and decides prognoses and immune microenvironment alterations.Cell cycle (Georgetown, Tex.) · 2022Article
- Transcriptomic Response to Acidosis Reveals Its Contribution to Bone Metastasis in Breast Cancer Cells.Cells · 2022Article
- Role of pH Regulatory Proteins and Dysregulation of pH in Prostate Cancer.Reviews of physiology, biochemistry and pharmacology · 2022Article
- High Expression of ATP6V1C2 Predicts Unfavorable Overall Survival in Patients With Colon Adenocarcinoma.Frontiers in genetics · 2022Article
- A novel four-gene of iron metabolism-related and methylated for prognosis prediction of hepatocellular carcinoma.Bioengineered · 2021Article
- Acid Microenvironment in Bone Sarcomas.Cancers · 2021Review
- Transcriptomic Profiling of Skeletal Muscle Reveals Candidate Genes Influencing Muscle Growth and Associated Lipid Composition in Portuguese Local Pig Breeds.Animals : an open access journal from MDPI · 2021Article
- V-ATPase Inhibition Decreases Mutant Androgen Receptor Activity in Castrate-resistant Prostate Cancer.Molecular cancer therapeutics · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
It is known that V-ATPases (vacuolar H+-ATPase) are involved in breast cancer growth and metastasis. Part of this action is similar to their role in osteoclasts, where they're involved in extracellular acidification and matrix destruction; however, the roles of their subunits in cancer cell proliferation, signaling, and other pro-tumor actions are not well established. Analysis of TCGA data shows that V-ATPase subunit Atp6v1c1 is overexpressed or amplified in 34% of human breast cancer cases, with a 2-fold decrease in survival at 12 years. Whereas other subunits, such as Atp6v1c2 and Atp6v0a3, are overexpressed or genomically amplified less often, 6% each respectively, and have less impact on survival. Experiments show that lentiviral-shRNA mediated ATP6v1c1 knockdown in 4T1 mouse mammary cancer cells significantly reduces orthotopic and intraosseous tumor growth. ATP6v1c1 knockdown also significantly reduces tumor stimulated bone resorption through osteoclastogenesis at the bone and metastasis in vivo, as well as V-ATPase activity, proliferation, and mTORC1 activation in vitro. To generalize the effects of ATP6v1c1 knockdown on proliferation and mTORC1 activation we used human cancer cell lines - MCF-7, MDA-MB-231, and MDA-MB-435s. ATP6V1C1 knockdown reduced cell proliferation and impaired mTORC1 pathway activation in cancer cells but not in the untransformed cell line C3H10T1/2. Our study reveals that V-ATPase activity may be mediated through mTORC1 and that ATP6v1c1 can be knocked down to block both V-ATPase and mTORC1 activity.
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Registered trials
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.