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

Mei Wang; Yang Liu; Jiahua Zou; Rui Yang; Fan Xuan; Yi Wang; Ning Gao; Hongjuan Cui

doi:10.18632/oncotarget.3367

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

Oncotarget. 2015 Apr 20;6(11):9517-30. doi: 10.18632/oncotarget.3367.

Authors

Mei Wang¹, Yang Liu^{2

3}, Jiahua Zou¹, Rui Yang¹, Fan Xuan¹, Yi Wang³, Ning Gao⁴, Hongjuan Cui¹

Affiliations

¹ State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
² Department of Respiration, the Third Hospital of Hebei Medical University, Shijiazhuang, China.
³ Cardiovascular Department, Second Affiliated Hospital of University of South China, Hengyang, China.
⁴ Department of Pharmacognosy, College of Pharmacy, Third Military Medical University, Chongqing, China.

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.

Keywords: TAZ; cell proliferation; colony formation; neuroblastoma.

Publication types

Comparative Study

MeSH terms

Animals
Cell Adhesion
Cell Division
Cell Line, Tumor
Connective Tissue Growth Factor / antagonists & inhibitors
Connective Tissue Growth Factor / biosynthesis
Connective Tissue Growth Factor / genetics
Gene Expression Regulation, Neoplastic*
Genes, sis
Heterografts
Humans
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / biosynthesis
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / physiology*
Mice
Mice, Inbred NOD
Mice, SCID
Molecular Targeted Therapy
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology*
Neuroblastoma / genetics
Neuroblastoma / pathology*
Prognosis
Proto-Oncogene Proteins c-sis / antagonists & inhibitors
Proto-Oncogene Proteins c-sis / biosynthesis
RNA Interference
RNA, Small Interfering / genetics
Recombinant Fusion Proteins / metabolism
Survival Rate
Trans-Activators
Transcription Factors
Transcriptional Coactivator with PDZ-Binding Motif Proteins
Transfection
Tumor Stem Cell Assay

Substances

CCN2 protein, human
Intracellular Signaling Peptides and Proteins
Neoplasm Proteins
Proto-Oncogene Proteins c-sis
RNA, Small Interfering
Recombinant Fusion Proteins
Trans-Activators
Transcription Factors
Transcriptional Coactivator with PDZ-Binding Motif Proteins
WWTR1 protein, human
Connective Tissue Growth Factor