title: Identification and characterization of the intercellular adhesion molecule-2 gene as a novel p53 target.
abstract: The p53 tumor suppressor inhibits cell growth through the activation of both cell cycle arrest and apoptosis, which maintain genome stability and prevent cancer development. Here, we report that intercellular adhesion molecule-2 (ICAM2) is transcriptionally activated by p53. Specifically, ICAM2 is induced by the p53 family and DNA damage in a p53-dependent manner. We identified a p53 binding sequence located within the ICAM2 gene that is responsive to wild-type p53, TAp73, and TAp63. In terms of function, we found that the ectopic expression of ICAM2 inhibited cancer cell migration and invasion. In addition, we demonstrated that silencing endogenous ICAM2 in cancer cells caused a marked increase in extracellular signal-regulated kinase (ERK) phosphorylation levels, suggesting that ICAM2 inhibits migration and invasion of cancer cells by suppressing ERK signaling. Moreover, ICAM2 is underexpressed in human cancer tissues containing mutant p53 as compared to those with wild-type p53. Notably, the decreased expression of ICAM2 is associated with poor survival in patients with various cancers. Our findings demonstrate that ICAM2 induction by p53 has a key role in inhibiting migration and invasion.
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, 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, Sapporo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.|Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogi
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.|Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakagaki
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Koyama
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Idogawa
authors.affiliation: Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hiratsuka
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D002070:Butadienes / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D000072160:Tumor Protein p73 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D002070:Butadienes; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D009570:Nitriles; D034741:RNA, Small Interfering; C495901:TP53 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ICAM2; cell invasion; cell migration; p53; p53 family