Rotoli Deborah, Morales Manuel, Ávila Julio, Maeso María Del Carmen, García María Del Pino, Mobasheri Ali, Martín-Vasallo Pablo
Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, Av. Astrofísico Sánchez s/n., 38206 La Laguna, Spain.
CNR-National Research Council, Institute of Endocrinology and Experimental Oncology (IEOS), Via Sergio Pansini 5, 80131 Naples, Italy.
Int J Mol Sci. 2017 Apr 22;18(4):891. doi: 10.3390/ijms18040891.
Scaffold proteins play pivotal roles in the regulation of signaling pathways, integrating external and internal stimuli to various cellular outputs. We report the pattern of cellular and subcellular expression of scaffoldins angiomotin-like 2 (AmotL2), FK506 binding protein 5 (FKBP51) and IQ motif containing GTPase-activating protein 1 (IQGAP1) in colorectal cancer (CRC) and metastases in liver resected after oxaliplatin-based chemotherapy (CT). Positive immunostaining for the three scaffoldins was found in most cells in healthy colon, tumor, healthy liver and metastasized liver. The patterns of expression of AmotL2, FKBP51 and IQGAP1 show the greatest variability in immune system cells and neurons and glia cells and the least in blood vessel cells. The simultaneous subcellular localization in tumor cells and other cell types within the tumor suggest an involvement of these three scaffoldins in cancer biology, including a role in Epithelial Mesenchymal Transition. The display in differential localization and quantitative expression of AmotL2, FKBP51, and IQGAP1 could be used as biomarkers for more accurate tumor staging and as potential targets for anti-cancer therapeutics by blocking or slowing down their interconnecting functions. Tough further research needs to be done in order to improve these assessments.
支架蛋白在信号通路调节中发挥关键作用，将外部和内部刺激整合为各种细胞输出。我们报告了支架蛋白血管动蛋白样2（AmotL2）、FK506结合蛋白5（FKBP51）和含IQ基序的GTP酶激活蛋白1（IQGAP1）在接受奥沙利铂化疗（CT）后切除的结直肠癌（CRC）及肝转移灶中的细胞和亚细胞表达模式。在健康结肠、肿瘤、健康肝脏和转移肝脏的大多数细胞中均发现这三种支架蛋白呈阳性免疫染色。AmotL2、FKBP51和IQGAP1的表达模式在免疫系统细胞、神经元和神经胶质细胞中变化最大，而在血管细胞中变化最小。这三种支架蛋白在肿瘤细胞和肿瘤内其他细胞类型中的同时亚细胞定位表明它们参与癌症生物学过程，包括在上皮-间质转化中发挥作用。AmotL2、FKBP51和IQGAP1在定位和定量表达上的差异表现可作为更准确肿瘤分期的生物标志物，以及通过阻断或减缓其相互连接功能作为抗癌治疗的潜在靶点。不过，为了改进这些评估，还需要进一步开展研究。
