Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid.
J Pharm Pharm Sci. 2013;16(2):177-89. doi: 10.18433/j3v59v.
Signal transduction pathways essential for the survival and viability of the cell and that frequently present aberrant expression or function in tumors are attractive targets for pharmacological intervention in human cancers. In this short review we will describe the regulation exerted by the calcium-receptor protein calmodulin (CaM) on signaling routes involving the family of ErbB receptors - highlighting the epidermal growth factor receptor (EGFR/ErbB1) and ErbB2 - and the adaptor protein Grb7, a downstream signaling component of these receptors. The signaling mechanism of the ErbB/Grb7 axis and the regulation exerted by CaM on this pathway will be described. We will present a brief overview of the current efforts to inhibit the hyperactivity of ErbB receptors and Grb7 in tumors. The currently available information on targeting the CaM-binding site of these signaling proteins will be analyzed, and the pros and cons of directly targeting CaM versus the CaM-binding domain of the ErbB receptors and Grb7 as potential anti-cancer therapy will be discussed.
信号转导通路对细胞的存活和活力至关重要，并且在肿瘤中经常表现出异常表达或功能，因此它们是人类癌症中药物干预的有吸引力的靶点。在这篇简短的综述中，我们将描述钙受体蛋白钙调蛋白（CaM）对涉及 ErbB 受体家族的信号通路的调节 - 重点介绍表皮生长因子受体（EGFR/ErbB1）和 ErbB2 - 以及衔接蛋白 Grb7，这些受体的下游信号成分。将描述 ErbB/Grb7 轴的信号机制以及 CaM 对该途径的调节。我们将简要概述目前抑制肿瘤中 ErbB 受体和 Grb7 过度活性的努力。将分析针对这些信号蛋白的 CaM 结合位点的现有信息，并讨论直接针对 CaM 与 ErbB 受体和 Grb7 的 CaM 结合域作为潜在抗癌疗法的优缺点。
