Ectopic expression of the microtubule-dependent motor protein Eg5 promotes pancreatic tumourigenesis.
Pancreatic cancer is a highly aggressive disease with a grim prognosis, due to its late diagnosis, propensity to rapidly metastasize, and resistance to therapy. The molecular events underlying this remain poorly defined. Here we report the overexpression and gene copy number gain of the microtubule-dependent motor protein Eg5 in human pancreatic cancer samples. We also show that Eg5 expression correlates with clinicopathological parameters of pancreatic cancer and promotes anchorage-independent cell growth and tumour formation in mice. In addition, Eg5 is up-regulated in pancreatic cancer cell lines and enhances cell proliferation in an ATPase activity-dependent manner. Our data further reveal that Eg5 overexpression causes the formation of multipolar spindles and multinucleation and induces the accumulation of polyploid cells. These findings demonstrate a role for Eg5 in pancreatic tumourigenesis and indicate a potential for targeting Eg5 in pancreatic cancer treatment.
Liu
Min
M
Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Wang
Xiuchao
X
Yang
Yunfan
Y
Li
Dengwen
D
Ren
He
H
Zhu
Qigang
Q
Chen
Qiang
Q
Han
Shuyong
S
Hao
Jihui
J
Zhou
Jun
J
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000209:etiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C470243:KIF11 protein, human; D020409:Molecular Motor Proteins; D000251:Adenosine Triphosphatases; D016547:Kinesins