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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Peng R,Jiang B,Ma J,Ma Z,Wan X,Liu H,Chen Z,Cheng Q,Chen R

doi

10.3892/or.2013.2723

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

2195-202

issue

5

eissn

1021-335X

issn

1791-2431

journal_volume

30

pub_type

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