Transcriptional co-activator TAZ sustains proliferation and tumorigenicity of neuroblastoma by targeting CTGF and PDGF-β

Abstract

Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial event in the pathogenesis of neuroblastoma is to promote proliferation of neuroblasts, which is closely related to poor survival. However, mechanisms for regulation of cell proliferation and tumorigenicity in neuroblastoma are not well understood. Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells. Inhibition of endogenous TAZ attenuated cell proliferation, colony formation and tumor development in neuroblastoma SK-N-AS cell, which could be rescued by re-introduction of TAZ into TAZ-knockdown cells. In addition, we found that overexpressing TAZ-mediated induction of CTGF and PDGF-β expression, cell proliferation and colony formation were inhibited by knocking down CTGF and PDGF-β with siRNA in TAZ-overexpressing cell. Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells. Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

The Hippo transducer TAZ promotes cell proliferation and tumor formation of glioblastoma cells through EGFR pathway

“…In recent years, enhanced expression of TAZ has been found in many malignant tumors, including gastric cancer, breast cancer, oral cancer, non-small cell lung cancer (NSCLC) and neuroblastoma, suggesting that TAZ is important for tumorigenesis [10–14]. In glioma, TAZ could regulate mesenchymal differentiation and tumor invasion [15].…”

“…Recently, TAZ was identified as a component of Hippo-LATS pathway, which is participated in transcriptional outcome to promote cell proliferation and inhibit apoptosis [10]. Most recently, enhanced expression of TAZ has been found in many malignant tumors, including gastric cancer, oral cancer, non-small cell lung cancer (NSCLC), breast cancer and neuroblastoma [11–14]. Overexpression of TAZ has been shown to promote cell proliferation and tumorigenesis in breast cancer, neuroblastoma and NSCLC cells, whereas knocking down TAZ expression suppresses cell proliferation and tumor formation, suggesting that TAZ may function as an oncogene in breast cancer, NSCLC and neuroblastoma.…”

MINA controls proliferation and tumorigenesis of glioblastoma by epigenetically regulating cyclins and CDKs via H3K9me3 demethylation

“…Transfection and infection were carried out as previously described. 31 Patient data analysis Patient and gene expression data were downloaded from the R2 database online (http://hgserver1.amc.nl/cgi-bin/r2/main.cgi). Using the R2 algorithm, Kaplan-Meier survival analysis was performed based on the high vs low MINA expression cutoff.…”

Down‐regulation of interferon regulatory factor 2 binding protein 2 suppresses gastric cancer progression by negatively regulating connective tissue growth factor

“…Activated YAP1 enters the nucleus, binds to TEAD4 and transcriptionally coactivates CTGF. It is an important oncogene related to cancer microenvironment and the progression of various cancers, including breast cancer, colorectal cancer, osteosarcoma, neuroblastoma and GC . In this study, the knockdown of IRF2BP2 in SGC‐7901 and BGC‐823 cells decreased the mRNA and protein levels of CTGF, suggesting that IRF2BP2 regulated CTGF expression at the transcriptional level.…”