Transcriptional co-activator TAZ sustains proliferation and tumorigenicity of neuroblastoma by targeting CTGF and PDGF-β.
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.
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
Mei
M
Wang
Department of Respiration, the Third Hospital of Hebei Medical University, Shijiazhuang, China.|Cardiovascular Department, Second Affiliated Hospital of University of South China, Hengyang, China.
Yang
Y
Liu
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
Jiahua
J
Zou
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
Rui
R
Yang
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
Fan
F
Xuan
Cardiovascular Department, Second Affiliated Hospital of University of South China, Hengyang, China.
Yi
Y
Wang
Department of Pharmacognosy, College of Pharmacy, Third Military Medical University, Chongqing, China.
Ning
N
Gao
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
Hongjuan
H
Cui
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020571:Genes, sis; D064593:Heterografts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015996:Survival Rate; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014162:Transfection; D014410:Tumor Stem Cell Assay
C526317:CCN2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D055513:Connective Tissue Growth Factor
TAZ; cell proliferation; colony formation; neuroblastoma