{"doi":"10.18632/oncotarget.28638","title":"A nanobody against the V-ATPase c subunit inhibits metastasis of 4T1-12B breast tumor cells to lung in mice","abstract":"// Zhen Li 2 , 4 , * , Mohammed A. Alshagawi 2 , 5 , * , Rebecca A. Oot 8 , Mariam K. Alamoudi 1 , 6 , Kevin Su 2 , 7 , Wenhui Li 2 , Michael P. Collins 3 , 9 , Stephan Wilkens 8 and Michael Forgac 1 , 2 , 3 1 Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA 2 Program in Pharmacology and Drug Development, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA 3 Program in Cellular, Molecular and Developmental Biology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA 4 Department of Cancer Immunology and Virology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA 5 Department of Pharmacology, University of Minnesota School of Medicine, MN 55455, USA 6 Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia 7 Korro Bio, Cambridge, MA 02139, USA 8 Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA 9 Foghorn Therapeutics, Cambridge, MA 02139, USA * These authors contributed equally to this work Correspondence to: Michael Forgac, email: michael.forgac@tufts.edu Keywords: vacuolar ATPase; breast cancer; invasion; tumor metastasis; tumor growth Received: June 28, 2024     Accepted: July 30, 2024     Published: August 14, 2024 Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT The vacuolar H + -ATPase (V-ATPase) is an ATP-dependent proton pump that functions to control the pH of intracellular compartments as well as to transport protons across the plasma membrane of various cell types, including cancer cells. We have previously shown that selective inhibition of plasma membrane V-ATPases in breast tumor cells inhibits the invasion of these cells in vitro . We have now developed a nanobody directed against an extracellular epitope of the mouse V-ATPase c subunit. We show that treatment of 4T1-12B mouse breast cancer cells with this nanobody inhibits V-ATPase-dependent acidification of the media and invasion of these cells in vitro . We further find that injection of this nanobody into mice implanted with 4T1-12B cells orthotopically in the mammary fat pad inhibits metastasis of tumor cells to lung. These results suggest that plasma membrane V-ATPases represent a novel therapeutic target to limit breast cancer metastasis.","journal":"Oncotarget","year":2024,"id":466165,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":975075,"name":"Mohammed A. Alshagawi","orcid":null,"position":1,"is_corresponding":false},{"id":663834,"name":"Rebecca A. Oot","orcid":"0000-0002-4680-8932","position":2,"is_corresponding":false},{"id":974577,"name":"Mariam K. Alamoudi","orcid":"0000-0001-7653-0401","position":3,"is_corresponding":false},{"id":975073,"name":"Kevin Su","orcid":null,"position":4,"is_corresponding":false},{"id":1297961,"name":"Wenhui Li","orcid":"0000-0003-3019-0450","position":5,"is_corresponding":false},{"id":244449,"name":"Michael P. 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