14-kDa phosphohistidine phosphatase and its role in human lung cancer cell migration and invasion.
14-kDa phosphohistidine phosphatase (PHP14) was the first protein histidine phosphatase to be discovered, but its biological function remains unclear. In our previous study, we found that it was associated with tumor invasion. Here, we investigated its role in lung cancer cell migration and invasion. Knockdown of PHP14 expression in highly metastatic lung cancer CL1-5 cells inhibited migration and invasion in vitro, but did not alter cell proliferation rates. Overexpression of PHP14 in NCI H1299 cells promoted migration and invasion in vitro, but again did not alter cell proliferation. To evaluate the metastatic properties of PHP14 in vivo, an experimental metastasis assay was performed. Experimental metastasis in vivo was extensively inhibited by PHP14 knockdown. To further examine the mechanism underlying the involvement of PHP14 in cell migration, invasion, and metastasis, a comparative proteomics analysis was performed. The differential protein expression profiles revealed that PHP14 was probably involved in cytoskeletal reorganization; this was further supported by actin filament (F-actin) staining. These results demonstrate for the first time that PHP14 may be functionally important in lung cancer cell migration and the invasion of lung cancer cells, mediated partly through modulation of actin cytoskeleton rearrangement.
Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Beijing Normal University, 19th Xinjiekouwai St., Beijing 100875, China.
Anjian
A
Xu
Jia
J
Hao
Zhao
Z
Zhang
Tian
T
Tian
Sanyi
S
Jiang
Juanting
J
Hao
Chuanjun
C
Liu
Lingyun
L
Huang
Xueyuan
X
Xiao
Dacheng
D
He
D000199:Actins / Q000378:metabolism; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000502:physiology*; D040901:Proteomics; D034622:RNA Interference
D000199:Actins; C504019:PHPT1 protein, human; D010744:Phosphoric Monoester Hydrolases