Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis.
Cyclin B1, a key component in the control of cell cycle progression from G(2) to M phase, has been implicated in tumorigenesis and the development of malignancy. However, the underlying mechanism by which cyclin B1 acts as an important oncogenic molecule remains largely unknown. Here we show that ectopic expression of cyclin B1 promotes cell proliferation, enhances cell motility and migration and results in increased ability of cells extravasating through the capillary endothelium. Interestingly, isogenic esophageal squamous cell carcinoma (ESCC) cells overexpressing cyclin B1 reveal strong invasive growth and high potential of metastasis to lung in xenograft mice. Suppression of cyclin B1 expression via small interfering RNA approach in high-metastatic esophagus carcinoma cells specifically inhibits their ability to metastasize from the primary ESCC to lung. Notably, altered expression of epithelial markers and mesenchymal markers were observed in the cells overexpressing cyclin B1, suggesting that cyclin B1 contributes to metastasis probably by promoting an epithelial-mesenchymal transition. These results establish a mechanistic link between cyclin B1 and ESCC metastasis and provide novel insight into understanding of cyclin B1 in the development of ESCC malignancy.
State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Yongmei
Y
Song
Chunling
C
Zhao
Lijia
L
Dong
Ming
M
Fu
Liyan
L
Xue
Zhen
Z
Huang
Tong
T
Tong
Zhuan
Z
Zhou
Amei
A
Chen
Zhihua
Z
Yang
Ning
N
Lu
Qimin
Q
Zhan
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019926:Cyclin B / Q000096:biosynthesis*; D056744:Cyclin B1; D004938:Esophageal Neoplasms / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation
C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1