Higgins Michael, Obaidi Ismael, McMorrow Tara
School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Oncol Lett. 2019 Mar;17(3):3041-3047. doi: 10.3892/ol.2019.9942. Epub 2019 Jan 17.
Primary cilia are microtubule-based organelles that are expressed on almost all mammalian cells. It has become apparent that these structures are important signaling hubs that serve crucial roles in Wnt, hedgehog, extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and Notch signaling pathways. A number of diseases have been found to involve dysfunctional primary cilia; collectively these diseases are called ciliopathies. In recent years, there has been more focus on the association between primary cilia and cancer, including renal, pancreatic and breast cancer. Numerous studies have demonstrated that various types of cancer cells fail to express cilia. Notably, it has also been indicated that a number of renal carcinogens induce a significant loss of cilia in renal epithelial cells. The present review focuses on the existing literature regarding primary cilia and their involvement with cancer signaling pathways, providing a brief overview of the structural features and functions of primary cilia, then discussing the evidence associating primary cilia with cancer, and presenting the available information on the ERK/MAPK, hedgehog and Wnt signaling pathways, and their involvement in primary cilia in association with cancer.
原发性纤毛是基于微管的细胞器,几乎在所有哺乳动物细胞上都有表达。显而易见,这些结构是重要的信号枢纽,在Wnt、刺猬信号通路、细胞外信号调节激酶(ERK)/丝裂原活化蛋白激酶(MAPK)和Notch信号通路中发挥关键作用。已发现许多疾病涉及原发性纤毛功能障碍;这些疾病统称为纤毛病。近年来,人们更加关注原发性纤毛与癌症之间的关联,包括肾癌、胰腺癌和乳腺癌。大量研究表明,各种类型的癌细胞无法表达纤毛。值得注意的是,也有研究表明,一些肾致癌物会导致肾上皮细胞中纤毛显著减少。本综述聚焦于关于原发性纤毛及其与癌症信号通路关系的现有文献,简要概述原发性纤毛的结构特征和功能,然后讨论原发性纤毛与癌症相关的证据,并介绍关于ERK/MAPK、刺猬信号通路和Wnt信号通路的现有信息,以及它们在原发性纤毛与癌症关联中的作用。