Forced downregulation of RACK1 inhibits glioma development by suppressing Src/Akt signaling activity.

Abstract

Glioma is the most common primary brain malignant tumor. Receptor for activated C-kinase 1 (RACK1) is widely expressed in the central nervous system, and regulates multiple cellular processes including cell survival, proliferation, migration and metastasis. However, the role of RACK1 in glioma has never been revealed. The present study, for the first time, showed that RACK1 expression was significantly higher in glioma tissues and cell lines when compared with that in normal brain tissues, and was positively associated with the malignancy of glioma. siRNA-induced RACK1 downregulation significantly suppressed the proliferation and invasion of human glioma U87 and CHG-5 cells, while it promoted their apoptosis by upregulating Bax expression and reducing Bcl-2 expression. Furthermore, forced downregulation of RACK1 notably inhibited tumor xenograft growth in nude mice. These findings suggest that RACK1 plays a critical role in the development and progression of glioma in vitro and in vivo. Moreover, siRNA-induced RACK1 downregulation markedly reduced the activity of Src/Akt signaling pathway, which plays an important role in the growth and behavior of human malignancies, indicating that siRNA-mediated RACK1 downregulation inhibited glioma probably via suppressing Src/Akt signaling activity. The present study highlighted the role of RACK1 in glioma, and demonstrated that RACK1 is a novel promising therapeutic target for glioma treatment.

• Authors: Renjun Peng, Bing Jiang, Jianrong Ma, Zhiming Ma, Xin Wan, Hongwei Liu, Zigui Chen, Quan Cheng, Rui Chen
• Journal: Oncology reports (Oncol Rep) Vol. 30 Issue 5 Pg. 2195-202 (Nov 2013) ISSN: 1791-2431 [Electronic] Greece
• PMID: 24008630 (Publication Type: Journal Article)

Chemical References

• Neoplasm Proteins
• RACK1 protein, human
• RNA, Small Interfering
• Receptors for Activated C Kinase
• Receptors, Cell Surface
• src-Family Kinases
• Proto-Oncogene Proteins c-akt
• GTP-Binding Proteins

Topics

• Animals
• Apoptosis (genetics)
• Brain Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• GTP-Binding Proteins (biosynthesis, genetics)
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, pathology)
• Humans
• Mice
• Molecular Targeted Therapy
• Neoplasm Proteins (biosynthesis, genetics)
• Proto-Oncogene Proteins c-akt (genetics)
• RNA, Small Interfering
• Receptors for Activated C Kinase
• Receptors, Cell Surface (biosynthesis, genetics)
• Signal Transduction (genetics)
• Xenograft Model Antitumor Assays
• src-Family Kinases (genetics)