Centonze Matteo, Saponaro Concetta, Mangia Anita
Functional Biomorphology Laboratory, IRCCS-Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Functional Biomorphology Laboratory, IRCCS-Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Transl Oncol. 2018 Apr;11(2):374-390. doi: 10.1016/j.tranon.2018.01.006. Epub 2018 Feb 20.
Na/H exchanger regulatory factor 1 (NHERF1) is a scaffold protein, with two tandem PDZ domains and a carboxyl-terminal ezrin-binding (EB) region. This particular sticky structure is responsible for its interaction with different molecules to form multi-complexes that have a pivotal role in a lot of diseases. In particular, its involvement during carcinogenesis and cancer progression has been deeply analyzed in different tumors. The role of NHERF1 is not unique in cancer; its activity is connected to its subcellular localization. The literature data suggest that NHERF1 could be a new prognostic/predictive biomarker from breast cancer to hematological cancers. Furthermore, the high potential of this molecule as therapeutical target in different carcinomas is a new challenge for precision medicine. These evidences are part of a future view to improving patient clinical management, which should allow different tumor phenotypes to be treated with tailored therapies. This article reviews the biology of NHERF1, its engagement in different signal pathways and its involvement in different cancers, with a specific focus on breast cancer. It also considers NHERF1 potential role during inflammation related to most human cancers, designating new perspectives in the study of this "Janus-like" protein.
钠/氢交换调节因子1（NHERF1）是一种支架蛋白，具有两个串联的PDZ结构域和一个羧基末端埃兹蛋白结合（EB）区域。这种特殊的粘性结构使其能够与不同分子相互作用，形成在许多疾病中起关键作用的多复合体。特别是，其在不同肿瘤的致癌过程和癌症进展中的作用已得到深入分析。NHERF1在癌症中的作用并非单一；其活性与其亚细胞定位有关。文献数据表明，NHERF1可能是从乳腺癌到血液系统癌症的一种新的预后/预测生物标志物。此外，该分子作为不同癌症治疗靶点的巨大潜力对精准医学来说是一个新挑战。这些证据是改善患者临床管理未来愿景的一部分，这应该能使不同肿瘤表型得到量身定制的治疗。本文综述了NHERF1的生物学特性、其在不同信号通路中的参与情况以及其在不同癌症中的作用，特别关注乳腺癌。文章还探讨了NHERF1在与大多数人类癌症相关的炎症过程中的潜在作用，为研究这种“两面神样”蛋白指明了新的方向。
