Transcriptional co-activator TAZ sustains proliferation and tumorigenicity of neuroblastoma by targeting CTGF and PDGF-β
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Mei Wang1,*, Yang Liu2,3,*, Jiahua Zou1, Rui Yang1, Fan Xuan1, Yi Wang3, Ning Gao4, Hongjuan Cui1
1State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China
2Department of Respiration, the Third Hospital of Hebei Medical University, Shijiazhuang, China
3Cardiovascular Department, Second Affiliated Hospital of University of South China, Hengyang, China
4Department of Pharmacognosy, College of Pharmacy, Third Military Medical University, Chongqing, China
*These authors have contributed equally to this work
Ning Gao, e-mail: [email protected]
Keywords: TAZ, cell proliferation, colony formation, neuroblastoma
Received: November 25, 2014 Accepted: February 11, 2015 Published: March 24, 2015
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.
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