Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2022; 13:784-784.

YAP promotes tumorigenesis and cisplatin resistance in neuroblastoma

Chao Yang, Juan Tan, Jun Zhu, Shan Wang and Guanghui Wei _

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Oncotarget. 2017; 8:37154-37163. https://doi.org/10.18632/oncotarget.16209

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Abstract

Chao Yang1,2,3, Juan Tan4, Jun Zhu2,3,5, Shan Wang1,2,3, Guanghui Wei2,3,6

1Department of Pediatric Surgical Oncology, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China

2China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China

3Chongqing Key Laboratory of Pediatrics, Chongqing, China

4Clinical Department of Children’s Hospital of Chongqing Medical University, Lijia Campus, Chongqing, China

5Department of Pathology, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China

6Department of Urology, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China

Correspondence to:

Guanghui Wei, email: [email protected], [email protected]

Keywords: neuroblastoma, YAP, cisplatin resistance

Received: December 15, 2016     Accepted: March 06, 2017     Published: March 15, 2017

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.


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