Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Human Anatomy, Histology and Embryology, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China.
Cancer Biol Med. 2020 May 15;17(2):270-281. doi: 10.20892/j.issn.2095-3941.2019.0420.
Four and a half LIM domains protein 1 (FHL1), as the name suggests, contains four and a half LIM domains capable of interacting with various molecules, including structural proteins, kinases, and transcriptional machinery. FHL1 contains a zinc-finger domain and performs diverse roles in regulation of gene transcription, cytoarchitecture, cell proliferation, and signal transduction. Several studies have validated the importance of FHL1 in muscle development, myopathy, and cardiovascular diseases. Mutations in the FHL1 gene are associated with various myopathies. Recently, FHL1 was identified as a major host factor for chikungunya virus (CHIKV) infection in both humans and mice. Based on more recent findings over the last decade, FHL1 is proposed to play a dual role in cancer progression. On the one hand, FHL1 expression is suppressed in several cancer types, which correlates with increased metastatic disease and decreased survival. Moreover, FHL1 is reported to inhibit tumor cell growth and migration by associating with diverse signals, such as TGF-β and ER, and therefore considered a tumor suppressor. On the other hand, FHL1 can function as an oncogenic protein that promotes tumor progression upon phosphorylation, reflecting complex roles in cancer. This review primarily focuses on the dual role and underlying mechanisms of action of FHL1 in human cancer progression and its clinical relevance.
四个半 LIM 结构域蛋白 1（FHL1），顾名思义，包含四个半 LIM 结构域，能够与各种分子相互作用，包括结构蛋白、激酶和转录机制。FHL1 包含一个锌指结构域，在基因转录、细胞结构、细胞增殖和信号转导的调节中发挥多种作用。几项研究已经证实了 FHL1 在肌肉发育、肌病和心血管疾病中的重要性。FHL1 基因的突变与各种肌病有关。最近，FHL1 被确定为人类和小鼠中基孔肯雅病毒（CHIKV）感染的主要宿主因子。基于过去十年的最新发现，FHL1 被认为在癌症进展中发挥双重作用。一方面，在几种癌症类型中，FHL1 的表达受到抑制，这与转移性疾病增加和生存率降低有关。此外，FHL1 被报道通过与 TGF-β 和 ER 等多种信号相关联来抑制肿瘤细胞的生长和迁移，因此被认为是一种肿瘤抑制因子。另一方面，FHL1 可以作为一种癌基因蛋白发挥作用，在磷酸化后促进肿瘤进展，反映了其在癌症中的复杂作用。这篇综述主要关注 FHL1 在人类癌症进展中的双重作用及其作用机制及其临床相关性。
