Faculty of Medicine, Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, People's Republic of China.
Key Laboratory for Regenerative Medicine of the Ministry of Education of China, Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, People's Republic of China.
Cell Mol Life Sci. 2018 May;75(10):1737-1756. doi: 10.1007/s00018-018-2755-6. Epub 2018 Feb 6.
Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR with cancer incidence in multiple cancers. We will then focus on the roles of CFTR in fundamental cellular processes including transformation, survival, proliferation, migration, invasion and epithelial-mesenchymal transition in cancer cells, highlighting the signaling pathways involved. Finally, the association of CFTR expression levels with patient prognosis, and the potential of CFTR as a cancer prognosis indicator in human malignancies will be discussed.
囊性纤维化跨膜电导调节因子(CFTR)的突变导致囊性纤维化,这是白种人中最常见的致死性隐性遗传疾病。CFTR 突变也与各种癌症的风险增加有关,但长期以来一直存在争议。最近的研究开始揭示,CFTR 不仅是一种离子通道,而且是癌症发生和发展的重要调节剂,已经确定了多种信号通路。在这篇综述中,我们将首先介绍临床发现,这些发现表明 CFTR 的基因突变或异常表达与多种癌症的癌症发病率之间存在相关性。然后,我们将重点介绍 CFTR 在癌症细胞中的基本细胞过程中的作用,包括转化、存活、增殖、迁移、侵袭和上皮-间充质转化,强调涉及的信号通路。最后,将讨论 CFTR 表达水平与患者预后的关系,以及 CFTR 作为人类恶性肿瘤中癌症预后指标的潜力。