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Oncotarget. 2017 Mar 15. doi: 10.18632/oncotarget.16209. [Epub ahead of print]

YAP promotes tumorigenesis and cisplatin resistance in neuroblastoma.

Yang C1,2,3, Tan J4, Zhu J2,3,5, Wang S1,2,3, Wei G2,3,6.

Author information

1
Department of Pediatric Surgical Oncology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
2
China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China.
3
Chongqing Key Laboratory of Pediatrics, Chongqing, China.
4
Clinical Department of Children's Hospital of Chongqing Medical University, Lijia Campus, Chongqing, China.
5
Department of Pathology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
6
Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

Abstract

The transcriptional co-activator Yes-associated protein (YAP) is essential for Hippo pathway-driven tumorigenesis in various cancers. However, the expression and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was highly expressed in Neuroblastoma (NB) and expression levels correlated with advanced tumor staging. Knockdown of YAP significantly impaired neuroblastoma proliferation, tumorigenesis, and invasion in vitro. Injection of the YAP inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor growth by efficiently downregulating YAP expression in tumors. Additionally, less proliferative and more apoptotic cells were found in the Peptide 17 treatment group. Furthermore, YAP inhibition significantly inhibited cisplatin-resistant neuroblastoma proliferation, tumorigenesis, and invasion in vitro. The combination of Peptide 17 with low-dose cisplatin efficiently impaired cisplatin-resistant NB subcutaneous tumor growth, being as effective as high-dose cisplatin. Notably, the combination therapy caused lesser liver toxicity in mice compared to the high-dose cisplatin treatment group. Collectively, this work identifies YAP as a novel regulator of neuroblastoma proliferation, tumorigenesis, and invasion and indicates that YAP is a potential therapeutic target for cisplatin-resistant neuroblastoma.

KEYWORDS:

YAP; cisplatin resistance; neuroblastoma

PMID:
28415761
DOI:
10.18632/oncotarget.16209
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