Background: Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) has been reported to interact with many cancer-related proteins. We recently identified a novel NHERF1 mutation (E43G) in breast tumours.
Materials And Methods: The candidates of NHERF1 mutation were identified in breast cancer tissues by polymerase chain reaction and DNA sequencing. Wild-type NHERF1 and E43G mutation were expressed in NHERF1-knockdown cells (MCF7ΔNHERF1) and low-NHERF1-expressing cells (SKMES-1). The effects of mutated NHERF1 on cell functions were examined using in vitro methods. Glutathione S-transferase pull-down assays and western blotting were performed to study the effects of NHERF1 mutation on its interaction with cancer-related proteins.
Results: Compared to wild-type NHERF1, expression of the mutated NHERF1 failed to suppress malignant traits in cancer cells, attenuated interaction of NHERF1 protein with epidermal growth factor receptor (EGFR), and inactivated its inhibition of EGF-induced Akt and extracellular regulated protein kinases (ERK) activation.
Conclusion: The results show the causal role of NHERF1 in the regulation of the EGFR pathway and the progression of breast cancer.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Noncanonical RGS14 structural determinants control hormone-sensitive NPT2A-mediated phosphate transport.
Biochem J
January 2025
University of Pittsburgh School of Medicine, Pittsburgh, United States.
The sodium phosphate cotransporter-2A (NPT2A) mediates basal and parathyroid hormone (PTH)- and fibroblast growth factor-23 (FGF23)-regulated phosphate transport in proximal tubule cells of the kidney. Both basal and hormone-sensitive transport require sodium hydrogen exchanger regulatory factor-1 (NHERF1), a scaffold protein with tandem PDZ domains, PDZ1 and PDZ2. NPT2A binds to PDZ1.
View Article and Find Full Text PDFStudies with Human-Induced Pluripotent Stem Cells Reveal That CTNS Mutations Can Alter Renal Proximal Tubule Differentiation.
Int J Mol Sci
November 2023
Biochemistry Department, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA.
Cystinosis is an autosomal recessive disease resulting from mutations in , which encodes for cystinosin, a proton-coupled cystine transporter that exports cystine from lysosomes. The major clinical form, infantile cystinosis, is associated with renal failure due to the malfunctioning of the renal proximal tubule (RPT). To examine the hypothesis that the malfunctioning of the cystinotic RPT arises from defective differentiation, human-induced pluripotent stem cells (hiPSCs) were generated from human dermal fibroblasts from an individual with infantile cystinosis, as well as a normal individual.
View Article and Find Full Text PDFMutations in an unrecognized internal NPT2A PDZ motif disrupt phosphate transport and cause congenital hypophosphatemia.
Biochem J
May 2023
Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A.
The Na+-dependent phosphate cotransporter-2A (NPT2A, SLC34A1) is a primary regulator of extracellular phosphate homeostasis. Its most prominent structural element is a carboxy-terminal PDZ ligand that binds Na+/H+ Exchanger Regulatory Factor-1 (NHERF1, SLC9A3R1). NHERF1, a multidomain PDZ protein, establishes NPT2A membrane localization and is required for hormone-inhibitable phosphate transport.
View Article and Find Full Text PDFThe Na -dependent phosphate cotransporter-2A (NPT2A, SLC34A1) is a primary regulator of extracellular phosphate homeostasis. Its most prominent structural element is a carboxy-terminal PDZ ligand that binds Na /H Exchanger Regulatory Factor-1 (NHERF1, SLC9A3R1). NHERF1, a multidomain PDZ protein,establishes NPT2A membrane localization and is required for hormone-sensitive phosphate transport.
View Article and Find Full Text PDFRelationship between clinical phenotype and in vitro analysis of 13 NPT2c/SCL34A3 mutants.
Sci Rep
January 2023
Université de Paris Cité, Faculté de Médecine, INSERM U1151, Paris, France.
Biallelic pathogenic variants in the SLC34A3 gene, encoding for the NPT2c cotransporter, cause Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH). However, the associated phenotype is highly variable. In addition, mice deleted for Slc34a3 exhibit a different phenotype compared to humans, without urinary phosphate leakage.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!