TY - JOUR
T1 - GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway
AU - Yu, Xiaoting
AU - Jin, Jing
AU - Zheng, Yanwen
AU - Zhu, Hua
AU - Xu, Hui
AU - Ma, Jun
AU - Lan, Qing
AU - Zhuang, Zhixiang
AU - Chen, Clark C.
AU - Li, Ming
N1 - Funding Information:
This work was supported with grants from the National Natural Sciences Foundation of China (82072802 and 81572480).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/2
Y1 - 2021/2
N2 - Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.
AB - Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.
UR - http://www.scopus.com/inward/record.url?scp=85101191046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101191046&partnerID=8YFLogxK
U2 - 10.1038/s41419-021-03492-3
DO - 10.1038/s41419-021-03492-3
M3 - Article
C2 - 33608513
AN - SCOPUS:85101191046
SN - 2041-4889
VL - 12
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 2
M1 - 203
ER -
