RRC ID 45389
Author Nagao-Kitamoto H, Setoguchi T, Kitamoto S, Nakamura S, Tsuru A, Nagata M, Nagano S, Ishidou Y, Yokouchi M, Kitajima S, Yoshioka T, Maeda S, Yonezawa S, Komiya S.
Title Ribosomal protein S3 regulates GLI2-mediated osteosarcoma invasion.
Journal Cancer Lett
Abstract It has been reported that GLI2 promotes proliferation, migration, and invasion of mesenchymal stem cell and osteosarcoma cells. To examine the molecular mechanisms of GLI2-mediated osteosarcoma metastasis, we performed a microarray analysis. The gene encoding ribosomal protein S3 (RPS3) was identified as a target of GLI2. Real-time PCR revealed that RPS3 was upregulated in osteosarcoma cell lines compared with normal osteoblast cells. Knockdown of GLI2 decreased RPS3 expression, whereas forced expression of a constitutively active form of GLI2 upregulated the expression of RPS3. RPS3 knockdown by siRNA decreased the migration and invasion of osteosarcoma cells. Although forced expression of constitutively active GLI2 increased the migration of human mesenchymal stem cells, knockdown of RPS3 reduced the up-regulated migration. In contrast, forced expression of RPS3 increased migration and invasion of osteosarcoma cells. Moreover, reduction of migration by GLI2 knockdown was rescued by forced expression of RPS3. Immunohistochemical analysis showed that RPS3 expression was increased in primary osteosarcoma lesions with lung metastases compared with those without. These findings indicate that GLI2-RPS3 signaling may be a marker of invasive osteosarcoma and a therapeutic target for patients with osteosarcoma.
Volume 356(2 Pt B)
Pages 855-61
Published 2015-1-28
DOI 10.1016/j.canlet.2014.10.042
PII S0304-3835(14)00653-3
PMID 25449781
MeSH Adolescent Adult Blotting, Western Bone Neoplasms / genetics Bone Neoplasms / metabolism Bone Neoplasms / pathology* Bone and Bones / metabolism* Bone and Bones / pathology Cell Adhesion Cell Movement Cell Proliferation Child Female Gene Expression Regulation, Neoplastic* Humans Immunoenzyme Techniques Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism* Male Middle Aged Neoplasm Invasiveness Nuclear Proteins / genetics Nuclear Proteins / metabolism* Osteosarcoma / genetics Osteosarcoma / metabolism Osteosarcoma / pathology* Promoter Regions, Genetic / genetics RNA, Messenger / genetics RNA, Small Interfering / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Ribosomal Proteins / antagonists & inhibitors Ribosomal Proteins / genetics Ribosomal Proteins / metabolism* Tumor Cells, Cultured Young Adult Zinc Finger Protein Gli2
IF 7.36
Times Cited 25
WOS Category ONCOLOGY
Resource
Human and Animal Cells HS-Os-1(RCB2229)