ArticleMolecular biology of the cell2012
NHERF1 acts as a molecular switch to program metastatic behavior and organotropism via its PDZ domains.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Optimizing Detection of Circulating Tumor Cells in Breast Cancer: Unveiling New Markers for Clinical Applications.International journal of molecular sciences · 2025Article
- The Biological Relevance of NHERF1 Protein in Gynecological Tumors.Frontiers in oncology · 2022Review
- Integrin-Linked Kinase Links Integrin Activation to Invadopodia Function and Invasion via the p(T567)-Ezrin/NHERF1/NHE1 Pathway.International journal of molecular sciences · 2021Article
- New roles of the NaAmerican journal of physiology. Renal physiology · 2020Review
- Prognostic and therapeutic implications of NHERF1 expression and regulation in colorectal cancer.Journal of surgical oncology · 2020Article
- Cause and effect of microenvironmental acidosis on bone metastases.Cancer metastasis reviews · 2019Review
- NHERF1 Between Promises and Hopes: Overview on Cancer and Prospective Openings.Translational oncology · 2018Review
- Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance.Oncogene · 2017Review
- EBP50 inhibits pancreatic cancer cell growth and invasion by targeting the β-catenin/E-cadherin pathway.Experimental and therapeutic medicine · 2015Article
- The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses.Molecular cancer · 2015Review
- PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism.Cancer biology & therapy · 2015Article
- ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.PloS one · 2013Article
- New conformational state of NHERF1-CXCR2 signaling complex captured by crystal lattice trapping.PloS one · 2013Article
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Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastatic cells are highly plastic for differential expression of tumor phenotype hallmarks and metastatic organotropism. The signaling proteins orchestrating the shift of one cell phenotype and organ pattern to another are little known. Na(+)/H(+) exchanger regulatory factor (NHERF1) is a molecular pathway organizer, PDZ-domain protein that recruits membrane, cytoplasmic, and cytoskeletal signaling proteins into functional complexes. To gain insight into the role of NHERF1 in metastatic progression, we stably transfected a metastatic breast cell line, MDA-MB-231, with an empty vector, with wild-type NHERF1, or with NHERF1 mutated in either the PDZ1- or PDZ2-binding domains to block their binding activities. We observed that NHERF1 differentially regulates the expression of two phenotypic programs through its PDZ domains, and these programs form the mechanistic basis for metastatic organotropism. The PDZ2 domain promotes visceral metastases via increased invadopodia-dependent invasion and anchorage-independent growth, as well as by inhibition of apoptosis, whereas the PDZ1 domain promotes bone metastases by stimulating podosome nucleation, motility, neoangiogenesis, vasculogenic mimicry, and osteoclastogenesis in the absence of increased growth or invasion. Collectively, these findings identify NHERF1 as an important signaling nexus for coordinating cell structure with metastatic behavior and identifies the "mesenchymal-to-vasculogenic" phenotypic transition as an essential step in metastatic progression.
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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.