ARK5 promotes glioma cell invasion, and its elevated expression is correlated with poor clinical outcome.
Poor prognosis of malignant gliomas is primarily attributed to their highly invasive nature. Despite the identification of new biomarkers and molecular targets for the improvement of the diagnosis, prognosis and treatment of glioma, the overall prognosis of the disease remains poor. This study is the first to show the significant upregulation of ARK5 paraffin-embedded archival glioma biopsies compared with those in adjacent non-cancerous brain tissues. Statistical analysis suggests that the upregulation of ARK5 correlates with the World Health Organization grade of glioma (P<0.001) and that patients with a high ARK5 level exhibit shorter survival time (P<0.01). In addition, ARK5 can promote glioma cell invasion by regulating cytoskeleton rearrangement and matrix metalloproteinase activation. ARK5 knockdown was found to reduce brain invasion in a glioma xenograft mouse model. Our results strongly suggest that ARK5 represents a novel and valuable biomarker to aid in the prediction of patient prognosis and is a potential therapeutic target against glioma.
Department of Pathology, Weifang Medical University, Weifang, Shandong, China.
Shijun
S
Lu
Na
N
Niu
Hua
H
Guo
Jinbao
J
Tang
Wenjun
W
Guo
Zhijun
Z
Liu
Lihong
L
Shi
Tongyi
T
Sun
Fenghua
F
Zhou
Hongli
H
Li
Jin
J
Zhang
Baogang
B
Zhang
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D054461:Lim Kinases / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011494:Protein Kinases / Q000032:analysis / Q000502:physiology*; D012097:Repressor Proteins / Q000032:analysis / Q000502:physiology*
D000199:Actins; D012097:Repressor Proteins; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; C470845:NUAK1 protein, human; C515892:LIMK1 protein, human; D054461:Lim Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9