Priority Research Papers:
p73 promotes glioblastoma cell invasion by directly activating POSTN (periostin) expression
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Vivien Landré1, Alexey Antonov1, Richard Knight1 and Gerry Melino1,2
1 Medical Research Council Toxicology Unit, Leicester LE1 9HN, UK
2 University of Rome Tor Vergata, 00133-Rome, Italy
Gerry Melino, email:
Keywords: periostin, p53 family, cell death, temozolomide, metastasis
Received: September 29, 2015 Accepted: January 18, 2016 Published: February 22, 2016
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.
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