title: p53 mediates the suppression of cancer cell invasion by inducing LIMA1/EPLIN.
abstract: The tumor suppressor gene p53 is frequently mutated in human cancer. p53 executes various functions, such as apoptosis induction and cell cycle arrest, by modulating transcriptional regulation. In this study, LIM domain and Actin-binding protein 1 (LIMA1) was identified as a target of the p53 family using a cDNA microarray. We also evaluated genome-wide occupancy of the p53 protein by performing chromatin immunoprecipitation-sequencing (ChIP-seq) and identified two p53 response elements in the LIMA1 gene. LIMA1 protein levels were increased by treatment with nutlin-3a, a small molecule that activates endogenous p53. In addition, LIMA1 expression was significantly downregulated in cancers compared with normal tissues. Knockdown of LIMA1 significantly enhanced cancer cell invasion and partially inhibited p53-induced suppression of cell invasion. Furthermore, low expression of LIMA1 in cancer patients correlated with decreased survival and poor prognosis. Thus, p53-induced LIMA1 inhibits cell invasion, and the downregulation of LIMA1 caused by p53 mutation results in decreased survival in cancer patients. Collectively, this study reveals the molecular mechanism of LIMA1 downregulation in various cancers and suggests that LIMA1 may be a novel prognostic predictor and a therapeutic target for cancer.
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Japan; Research Fellow of Japan Society for the Promotion of Science, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Japan. Electronic address: idogawa@sapmed.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Idogawa
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Japan. Electronic address: tokino@sapmed.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C403263:LIMA1 protein, human; D016159:Tumor Suppressor Protein p53
keywords: EPLIN; Invasion; LIMA1; Prognosis; p53