Porębska Natalia, Latko Marta, Kucińska Marika, Zakrzewska Małgorzata, Otlewski Jacek, Opaliński Łukasz
Department of Protein Engineering, Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
J Clin Med. 2018 Dec 20;8(1):7. doi: 10.3390/jcm8010007.
Fibroblast growth factor receptors (FGFRs) in response to fibroblast growth factors (FGFs) transmit signals across the cell membrane, regulating important cellular processes, like differentiation, division, motility, and death. The aberrant activity of FGFRs is often observed in various diseases, especially in cancer. The uncontrolled FGFRs' function may result from their overproduction, activating mutations, or generation of FGFRs' fusion proteins. Besides their typical subcellular localization on the cell surface, FGFRs are often found inside the cells, in the nucleus and mitochondria. The intracellular pool of FGFRs utilizes different mechanisms to facilitate cancer cell survival and expansion. In this review, we summarize the current stage of knowledge about the role of FGFRs in oncogenic processes. We focused on the mechanisms of FGFRs' cellular trafficking-internalization, nuclear translocation, and mitochondrial targeting, as well as their role in carcinogenesis. The subcellular sorting of FGFRs constitutes an attractive target for anti-cancer therapies. The blocking of FGFRs' nuclear and mitochondrial translocation can lead to the inhibition of cancer invasion. Moreover, the endocytosis of FGFRs can serve as a tool for the efficient and highly selective delivery of drugs into cancer cells overproducing these receptors. Here, we provide up to date examples how the cellular sorting of FGFRs can be hijacked for selective cancer treatment.
成纤维细胞生长因子受体(FGFRs)在响应成纤维细胞生长因子(FGFs)时跨细胞膜传递信号,调节重要的细胞过程,如分化、分裂、运动和死亡。FGFRs的异常活性在各种疾病中经常被观察到,尤其是在癌症中。FGFRs功能失控可能是由于其过度产生、激活突变或FGFRs融合蛋白的产生。除了在细胞表面的典型亚细胞定位外,FGFRs还经常在细胞内、细胞核和线粒体中被发现。细胞内的FGFRs池利用不同机制促进癌细胞的存活和增殖。在本综述中,我们总结了目前关于FGFRs在致癌过程中作用的知识阶段。我们重点关注FGFRs的细胞转运机制——内化、核转位和线粒体靶向,以及它们在致癌作用中的作用。FGFRs的亚细胞分选构成了抗癌治疗的一个有吸引力的靶点。阻断FGFRs的核转位和线粒体转位可导致癌症侵袭的抑制。此外,FGFRs的内吞作用可作为一种工具,用于将药物高效且高度选择性地递送至过度产生这些受体的癌细胞中。在此,我们提供了最新的例子,说明如何利用FGFRs的细胞分选进行选择性癌症治疗。