title: p73 promotes glioblastoma cell invasion by directly activating POSTN (periostin) expression.
abstract: Glioblastoma Multiforme is one of the most highly metastatic cancers and constitutes 70% of all gliomas. Despite aggressive treatments these tumours have an exceptionally bad prognosis, mainly due to therapy resistance and tumour recurrence. Here we show that the transcription factor p73 confers an invasive phenotype by directly activating expression of POSTN (periostin, HGNC:16953) in glioblastoma cells. Knock down of endogenous p73 reduces invasiveness and chemo-resistance, and promotes differentiation in vitro. Using chromatin immunoprecipitation and reporter assays we demonstrate that POSTN, an integrin binding protein that has recently been shown to play a major role in metastasis, is a transcriptional target of TAp73. We further show that POSTN overexpression is sufficient to rescue the invasive phenotype of glioblastoma cells after p73 knock down. Additionally, bioinformatics analysis revealed that an intact p73/ POSTN axis, where POSTN and p73 expression is correlated, predicts bad prognosis in several cancer types. Taken together, our results support a novel role of TAp73 in controlling glioblastoma cell invasion by regulating the expression of the matricellular protein POSTN.
authors.affiliation: Medical Research Council Toxicology Unit, Leicester LE1 9HN, UK.
authors.forename: Vivien
authors.initials: V
authors.lastname: Landré
authors.affiliation: Medical Research Council Toxicology Unit, Leicester LE1 9HN, UK.
authors.forename: Alexey
authors.initials: A
authors.lastname: Antonov
authors.affiliation: Medical Research Council Toxicology Unit, Leicester LE1 9HN, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Knight
authors.affiliation: Medical Research Council Toxicology Unit, Leicester LE1 9HN, UK.|University of Rome Tor Vergata, Rome 00133, Italy.
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
mesh_terms: D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73 / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73
keywords: cell death; metastasis; p53 family; periostin; temozolomide