TY - JOUR
T1 - p73 promotes glioblastoma cell invasion by directly activating POSTN (periostin) expression
AU - Landré, Vivien
AU - Antonov, Alexey
AU - Knight, Richard
AU - Melino, Gerry
PY - 2016/3/15
Y1 - 2016/3/15
N2 - 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.
AB - 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.
KW - Cell death
KW - Metastasis
KW - p53 family
KW - Periostin
KW - Temozolomide
UR - http://www.scopus.com/inward/record.url?scp=84962799595&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962799595&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.7600
DO - 10.18632/oncotarget.7600
M3 - Article
AN - SCOPUS:84962799595
VL - 7
SP - 11785
EP - 11802
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 11
ER -