Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo

被引:46
作者
Lu, Jian [1 ,2 ,3 ]
Chen, Min [1 ,3 ]
Tao, Zhenhua [2 ]
Gao, Sumeng [3 ]
Li, Yang [1 ]
Cao, Yu [1 ]
Lu, Chun [4 ]
Zou, Xiaoping [1 ,3 ]
机构
[1] Nanjing Med Univ, Dept Gastroenterol, Nanjing Drum Tower Hosp, Clin Coll, Nanjing 210008, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Wuxi Hosp 2, Dept Gastroenterol, Wuxi 214002, Peoples R China
[3] Nanjing Univ, Med Sch, Affiliated Drum Tower Hosp, Dept Gastroenterol, Nanjing 210008, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Dept Microbiol, Nanjing 211116, Jiangsu, Peoples R China
基金
美国国家科学基金会;
关键词
SLC1A5; gastric cancer; cell proliferation; cell motility; GLUTAMINE UPTAKE; CLINICOPATHOLOGICAL SIGNIFICANCE; ASCT2; LAT1; METABOLISM; EXPRESSION; TRANSPORT;
D O I
10.18632/oncotarget.19479
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aims: To investigate the oncogenic effects of SLC1A5 on gastric cancer development in vitro and in vivo. Methods: The expression level of SLC1A5 was detected in 70 gastric cancer paraffin-embedded tissues by immunohistochemistry and also was detected in gastric cancer cell lines by qRT-PCR and western blotting analysis. The effects of knockdown SLC1A5 were analyzed on cell proliferation, cell cycle, the ability of cell migration and invasion and growth signaling pathway in vitro. By using subcutaneous xenograft mouse, the importance of SLC1A5 expression was assessed for both successful engraftment and growth of gastric cancer cells in vivo. Results: SLC1A5 was up-regulated in gastric cancer tissues and was correlated with malignant features such as deeper local invasion, higher lymph node metastasis, advanced TNM stages and higher Ki-67 expression. Knockdown SLC1A5 in gastric cancer cells suppressed cell proliferation, caused G0/G1 arrest and inhibited cell invasion as well as migration partly by inactivated mTOR/p-70S6K1 signaling pathway in vitro. Furthermore, in vivo experiments indicated that suppression of SLC1A5 could inhibit relative volume of xenografted tumor. Conclusions: Our results suggested that SLC1A5 might be considered as a new biomarker and also as a potential therapeutic target in gastric cancer.
引用
收藏
页码:76458 / 76467
页数:10
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