Open AccessOverexpression of geranylgeranyl diphosphate synthase contributes to tumour metastasis and correlates with poor prognosis of lung adenocarcinoma
Author(s) -
Wang Xiaoxia,
Xu Wujian,
Zhan Ping,
Xu Tianxiang,
Jin Jiajia,
Miu Yingying,
Zhou Zejun,
Zhu Qingqing,
Wan Bing,
Xi Guangmin,
Ye Liang,
Liu Yafang,
Gao Jianwei,
Li Huijuan,
Lv Tangfeng,
Song Yong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13493
Subject(s) - cancer research , metastasis , adenocarcinoma , biology , gene knockdown , epithelial–mesenchymal transition , a549 cell , apoptosis , cancer , biochemistry , genetics
Abstract This study aimed to evaluate the biological role of geranylgeranyl diphosphate synthase ( GGPPS ) in the progression of lung adenocarcinoma. GGPPS expression was detected in lung adenocarcinoma tissues by qRT ‐ PCR , tissue microarray ( TMA ) and western blotting. The relationships between GGPPS expression and the clinicopathological characteristics and prognosis of lung adenocarcinoma patients were assessed. GGPPS was down‐regulated in SPCA ‐1, PC 9 and A549 cells using si RNA and up‐regulated in A549 cells using an adenoviral vector. The biological roles of GGPPS in cell proliferation, apoptosis, migration and invasion were determined by MTT and colony formation assays, flow cytometry, and transwell and wound‐healing assays, respectively. In addition, the regulatory roles of GGPPS on the expression of several epithelial‐mesenchymal transition ( EMT ) markers were determined. Furthermore, the Rac1/Cdc42 prenylation was detected after knockdown of GGPPS in SPCA ‐1 and PC 9 cells. GGPPS expression was significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Overexpression of GGPPS was correlated with large tumours, high TNM stage, lymph node metastasis and poor prognosis in patients. Knockdown of GGPPS inhibited the migration and invasion of lung adenocarcinoma cells, but did not affect cell proliferation and apoptosis. Meanwhile, GGPPS inhibition significantly increased the expression of E‐cadherin and reduced the expression of N‐cadherin and vimentin in lung adenocarcinoma cells. In addition, the Rac1/Cdc42 geranylgeranylation was reduced by GGPPS knockdown. Overexpression of GGPPS correlates with poor prognosis of lung adenocarcinoma and contributes to metastasis through regulating EMT .