Four and a half LIM domains protein 1 can be as a double-edged sword in cancer progression

Xiaofan Wei, Hongquan Zhang

Abstract


Four and a half LIM domains protein 1 (FHL1), as the name suggests, contains four and a half LIM domains capable of interactingwith various molecules, including structural proteins, kinases, and transcriptional machinery. FHL1 contains a zinc-finger domainand performs diverse roles in regulation of gene transcription, cytoarchitecture, cell proliferation, and signal transduction. Severalstudies have validated the importance of FHL1 in muscle development, myopathy, and cardiovascular diseases. Mutations in theFHL1 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 dualrole in cancer progression. On the one hand, FHL1 expression is suppressed in several cancer types, which correlates with increasedmetastatic disease and decreased survival. Moreover, FHL1 is reported to inhibit tumor cell growth and migration by associating withdiverse signals, such as TGF-β and ER, and therefore considered a tumor suppressor. On the other hand, FHL1 can function as anoncogenic protein that promotes tumor progression upon phosphorylation, reflecting complex roles in cancer. This review primarilyfocuses on the dual role and underlying mechanisms of action of FHL1 in human cancer progression and its clinical relevance.

Cite this article as: Wei X and Zhang H. Four and a half LIM domains protein1 can be as a double-edged sword in cancer progression. Cancer Biol Med.2020; 17: 270-281. doi: 10.20892/j.issn.2095-3941.2019.0420


Keywords


Four and a half LIM protein 1 (FHL1); metastasis; tumor cell growth

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