Phosphorylation of NHERF1 S279 and S301 differentially regulates breast cancer cell phenotype and metastatic organotropism
| Autor: | Séverine Marionneau-Lambot, Emeline Bon, Stefania Cannone, Sébastien Roger, Thibauld Oullier, Roseline Guibon, Maria Raffaella Greco, Rosa Rubino, Rosa Angela Cardone, Manuel Bernabe-Garcia, Gaëlle Fromont, Maria-Luisa Cayuela, Stephan J. Reshkin, Loredana Ciaccia, Lorenzo Guerra |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Scaffold protein Sodium-Hydrogen Exchangers PDZ domain Breast Neoplasms Biology Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Animals Humans Neoplasm Invasiveness Vasculogenic mimicry Neoplasm Metastasis Phosphorylation Molecular Biology Zebrafish Sodium-Hydrogen Exchanger 1 Hydrogen-Ion Concentration Phosphoproteins Xenograft Model Antitumor Assays Phenotype Cell biology Gene Expression Regulation Neoplastic Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Molecular Medicine Female Mutant Proteins Signal transduction Reprogramming Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1865:26-37 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2018.10.017 |
| Popis: | Metastatic cancer cells are highly plastic for the expression of different tumor phenotype hallmarks and organotropism. This plasticity is highly regulated but the dynamics of the signaling processes orchestrating the shift from one cell phenotype and metastatic organ pattern to another are still largely unknown. The scaffolding protein NHERF1 has been shown to regulate the expression of different neoplastic phenotypes through its PDZ domains, which forms the mechanistic basis for metastatic organotropism. This reprogramming activity was postulated to be dependent on its differential phosphorylation patterns. Here, we show that NHERF1 phosphorylation on S279/S301 dictates several tumor phenotypes such as in vivo invasion, NHE1-mediated matrix digestion, growth and vasculogenic mimicry. Remarkably, injecting mice with cells having differential NHERF1 expression and phosphorylation drove a shift from the predominantly lung colonization (WT NHERF1) to predominately bone colonization (double S279A/S301A mutant), indicating that NHERF1 phosphorylation also acts as a signaling switch in metastatic organotropism. |
| Databáze: | OpenAIRE |
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