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p73 promotes glioblastoma cell invasion by directly activating POSTN (periostin) expression

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posted on 2016-06-20, 13:44 authored by Vivien Landré, Alexey Antonov, Richard Knight, Gerry Melino
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.

Funding

This work has been supported by the Medical Research Council, UK; grants from Associazione Italiana per la Ricerca contro il Cancro (AIRC; 2011-IG11955; 5xmille MCO #9979) and Fondazione Roma (NCD), Min. Salute to Istituto Dermopatico dell’Immacolata/Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS RF08 c.15, RF07 c.57) to GM.

History

Citation

Oncotarget, Vol. 7, No. 11

Version

  • VoR (Version of Record)

Published in

Oncotarget

Publisher

Impact Journals

eissn

1949-2553

Acceptance date

2016-01-18

Available date

2016-06-20

Publisher version

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=7600

Language

en

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