PLK1 promotes epithelial-mesenchymal transition and metastasis of gastric carcinoma cells.
Cancer cell epithelial-mesenchymal transition (EMT) is the crucial event for cancer progression and plays a vital role in the metastasis of cancer cells. Activation of Polo-like kinase 1 (PLK1) signaling has been implicated as the critical event in several tumor metastasis and EMT, however, whether PLK1 participates in gastric carcinoma metastasis and EMT still remains unclear. For this study, we elucidated the potential physiological function of PLK1 in the metastasis of gastric tumors, as well its distinct role in cells EMT and subsequently determined the mechanism involved in PLK1 regulated. Immunoblotting assay and Oncomine data mining analysis indicated that PLK1 expression was highly up-regulated in gastric carcinoma. Kaplan-Meier survival analysis for the relationship between survival outcomes and PLK1 expression in gastric carcinoma was performed with an online Kaplan-Meier plotter (http://kmplot.com/analysis/). Over-expression of PLK1 in gastric cancer cells SGC-7901 and MKN-28 significantly promoted cells profound morphological changes and enhanced metastatic ability of tumor cells. On the contrary, silencing of PLK1 induced mesenchymal epithelial transition (MET)-like morphological and inhibited the metastatic process. Furthermore, we found that the metastatic characters promoting effects of PLK1 in gastric carcinoma was related to the activation of protein kinase B (AKT). Our mechanistic investigations revealed that AKT inhibition reversed PLK1-induced EMT, blocked gastric carcinoma cells invasiveness and metastasis. Additionally, over-expression of AKT promoted the migratory and invasion ability of the two cell lines, which was disrupted by PLK1 down-regulation. To conclude, our findings demonstrate that PLK1 accelerates the metastasis and epithelial-mesenchyme transition of gastric cancer cells through regulating the AKT pathway.
Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan University Wuhan, Hubei, China.
Xiao Peng
XP
Cai
Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan University Wuhan, Hubei, China.
Liang Dong
LD
Chen
Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan University Wuhan, Hubei, China.
Hai Bin
HB
Song
Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan University Wuhan, Hubei, China.
Chun Xiao
CX
Zhang
Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan University Wuhan, Hubei, China.
Ze Wei
ZW
Yuan
Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan University Wuhan, Hubei, China.
Zhen Xian
ZX
Xiang
EMT; PLK1; gastric carcinoma; metastasis