The prognostic value of the Na⁺/H⁺ exchanger regulatory factor 1 (NHERF1) protein in cancer

Issue title: An update from the Romanian international meeting “Cancer molecular pathobiology in the clinics: Highlights”

Guest editors: Ioana Berindan Neagoex and Angelo Paradisoy

Article type: Research Article

Authors: Saponaro, Concetta^a | Malfettone, Andrea^a | Dell'Endice, Teresa Stefania^a | Brunetti, Anna Elisabetta^b | Achimas-Cadariu, Patriciu^{c; d} | Paradiso, Angelo^b | Mangia, Anita^{a; *}

Affiliations: [a] Functional Biomorphology Laboratory, National Cancer Research Centre, Istituto Tumori “Giovanni Paolo II”, Bari, Italy | [b] Scientific Direction, National Cancer Research Centre, Istituto Tumori “Giovanni Paolo II”, Bari, Italy | [c] Department of Surgical Oncology The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj Napoca, Romania | [d] Department of Surgical Oncology and Gynecological Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania | [x] The University of Medicine and Pharmacy Iuliu Hatieganu, Cluj, Napoca, Romania | [y] National Cancer Research Center, Istituto Tumori G Paolo II, IRCCS, Bari, Italy

Correspondence: [*] Corresponding author: Anita Mangia, Functional Biomorphology Laboratory, National Cancer Research Centre, Istituto Tumori “Giovanni Paolo II”, Bari, Italy. E-mail: [email protected].

Abstract: NHERF1 (Na+/H+ exchanger regulatory factor) is a scaffolding protein, consists of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region. NHERF1 recruits macromolecular complexes at the apical membrane of epithelial cells in many epithelial tissues. It is involved in trafficking and regulation of transmembrane ion transporters and G protein-coupled receptors. Further, NHERF1 also linked other molecules involved in cell growth and cancer progression, such as PDGFR, PTEN, β-catenin, EGFR and HER2/neu. In this review, we focus on the role of NHERF1 during cancer development. Evidences of its involvement in cancer development are present in hepatocellular carcinoma, schwannoma, glioblastoma, colorectal cancer and particularly in breast cancer. Recent findings obtained from our laboratory show that cytoplasmic NHERF1 expression increases gradually in breast cancer during carcinogenesis, and its overexpression is associated with aggressive clinical parameters, unfavourable prognosis, and increased tumor hypoxia. Interestingly, also nuclear NHERF1 expression seems to play a role both in carcinogenesis and progression of colorectal cancer. These data suggest that NHERF1 could be a new biomarker of advanced malignancies.

Keywords: NHERF1, cancers, carcinogenesis, cancer progression

DOI: 10.3233/CBM-130329

Journal: Cancer Biomarkers, vol. 14, no. 2-3, pp. 177-184, 2014