title: The FHL2 regulation in the transcriptional circuitry of human cancers.
abstract: The Four-and-a-half LIM (FHL)-only protein is a subfamily of protein members under the LIM-only protein family. These proteins are identified by their characteristic four and a half cysteinerich LIM homeodomain. Five members have been categorized into the FHL subfamily, which are FHL1, FHL2, FHL3, FHL4 and activator of CREM in testis (ACT) in human. FHL2 is amongst the most examined members within the family. Fhl2, the gene that code for the protein, is transcriptionally regulated by diverse types of transcription factors, for example, p53, serum response factor (SRF), and specificity protein 1 (Sp1). The expression of FHL2 is found in different tissues and organs and has been reported as a critical participant influencing the wide types of cancer such as breast cancer, gastrointestinal (GI) cancers, liver cancer and prostate cancer. The expression profile of FHL2 appeared to have a significant functional role in the carcinogenesis of these cancers which are mediated by different types of transcription factor including both tumor suppressors and inducers. In this review, we will first describe the molecular network governing FHL2 expression, which focus on the transcription factors conveying FHL2-initiated responses. In the second part, FHL2-linked cancers and the underlying molecular machinery will be discussed. Factors other than transcriptional regulation which may involve the cancer progression such as mutations of fhl2 and posttranslational modifications of the protein will also be mentioned.
authors.affiliation: School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Cyanne Ye
authors.initials: CY
authors.lastname: Cao
authors.affiliation: School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China. Electronic address: simon_mok@cuhk.edu.hk.
authors.forename: Simon Wing-Fai
authors.initials: SW
authors.lastname: Mok
authors.affiliation: School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Vincent Wing-Sang
authors.initials: VW
authors.lastname: Cheng
authors.affiliation: School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Stephen Kwok-Wing
authors.initials: SK
authors.lastname: Tsui
mesh_terms: D005260:Female; D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D060066:Protein Interaction Maps; D026362:Serum Response Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C105987:FHL2 protein, human; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; C476858:SRF protein, human; D026362:Serum Response Factor; D014157:Transcription Factors
keywords: Bioinformatics; Breast cancer; Four-and-a-half Lim (FHL2); Gastrointestinal cancer (GI cancer); Hepatocellular carcinoma (HCC); Liver cancer; Nucleus translocation; Prostate cancer; Serum response factor (SRF); Specificity protein 1 (SP1); Transcriptional regulation; p53