NHERF1/EBP50 in Breast Cancer: Clinical PerspectivesBellizzi A.a · Malfettone A.a · Cardone R.A.b · Mangia A.a
a Clinical Experimental Oncology Laboratory, National Cancer Centre, Bari, b Department of General and Environmental Physiology, University of Bari, Italy, Both authors equally contributed to this work. Corresponding Author
Anita Mangia, PhD, Clinical Experimental Oncology Laboratory, National Cancer Centre, Via Hahnemann, 10, 70126 Bari, Italy, Tel. +39 0805555527, firstname.lastname@example.org
Na+/H+ exchanger regulatory factor 1 (NHERF1) is a postsynaptic density 95/disc-large/zona occludens (PDZ) domain-containing protein that recruits membrane receptors/transporters and cytoplasmic signaling proteins into functional complexes. NHERF1 expression has been demonstrated to be altered in breast cancer, but its role in mammary cancerogenesis and progression remains still undefined. In this paper, we review what is known on the pathological role and the potential clinical application of NHERF1 protein in breast cancer. Recent evidence shows that an increased cytoplasmic expression of NHERF1 suggests a key role of its localization/compartmentalization in defining cancerogenesis, progression, and invasion. NHERF1 overexpression is associated with increasing tumor cytohistological grade, aggressive clinical behavior, unfavorable prognosis, and increased tumor hypoxia. Moreover, NHERF1 co-localizes with the oncogenic receptor HER2/neu in HER2/neu-overexpressing carcinoma and in distant metastases. These data make NHERF1 also a potential candidate of clinical relevance for anti-HER2/neu therapy.
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