The transcription factor FOXO4 is down-regulated and inhibits tumor proliferation and metastasis in gastric cancer.
The transcription factor FOXO4 is down-regulated and inhibits tumor proliferation and metastasis in gastric cancer.
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转录因子FOXO4下调并抑制胃癌肿瘤增殖和转移
DOI：
10.1186/1471-2407-14-378
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发表时间：
2014-05-28
期刊：
影响因子：
3.8
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Su L;Liu X;Chai N;Lv L;Wang R;Li X;Nie Y;Shi Y;Fan D
foxo4是FOXO转录因子家族中的一员，是目前研究的热点。其在胃癌中的作用和功能尚未完全阐明。本研究旨在探讨FOXO4在胃癌中的表达谱及其对胃癌细胞生长和转移的影响。方法采用免疫组化、Western blotting和qRT-PCR检测胃癌细胞和组织中FOXO4的表达。采用细胞生物学试验、皮下致瘤性试验和尾静脉转移试验结合慢病毒构建，检测FOXO4对体外和体内胃癌增殖转移的影响。采用共聚焦和qRT-PCR方法探讨其作用机制。结果FOXO4在大多数胃癌组织和各种人胃癌细胞系中的表达均显著降低。在体外实验中，上调FOXO4可抑制胃癌细胞株的生长和转移，体内实验中，FOXO4可显著抑制肿瘤生长和肝、肺转移，而下调FOXO4并结合特异性sirna可促进胃癌细胞株的生长和转移。此外，我们发现上调FOXO4可诱导G1阻滞和S期减少，并下调vimentin的表达。结论FOXO4表达缺失有助于胃癌的生长和转移，可能是胃癌的潜在治疗靶点。
BackgroundFOXO4, a member of the FOXO family of transcription factors, is currently the focus of intense study. Its role and function in gastric cancer have not been fully elucidated. The present study was aimed to investigate the expression profile of FOXO4 in gastric cancer and the effect of FOXO4 on cancer cell growth and metastasis.MethodsImmunohistochemistry, Western blotting and qRT-PCR were performed to detect the FOXO4 expression in gastric cancer cells and tissues. Cell biological assays, subcutaneous tumorigenicity and tail vein metastatic assay in combination with lentivirus construction were performed to detect the impact of FOXO4 to gastric cancer in proliferation and metastasis in vitro and in vivo. Confocal and qRT-PCR were performed to explore the mechanisms.ResultsWe found that the expression of FOXO4 was decreased significantly in most gastric cancer tissues and in various human gastric cancer cell lines. Up-regulating FOXO4 inhibited the growth and metastasis of gastric cancer cell lines in vitro and led to dramatic attenuation of tumor growth, and liver and lung metastasis in vivo, whereas down-regulating FOXO4 with specific siRNAs promoted the growth and metastasis of gastric cancer cell lines. Furthermore, we found that up-regulating FOXO4 could induce significant G1 arrest and S phase reduction and down-regulation of the expression of vimentin.ConclusionOur data suggest that loss of FOXO4 expression contributes to gastric cancer growth and metastasis, and it may serve as a potential therapeutic target for gastric cancer.
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影响因子：
3.7
作者：
Kajita Y;Kato T Jr;Tamaki S;Furu M;Takahashi R;Nagayama S;Aoyama T;Nishiyama H;Nakamura E;Katagiri T;Nakamura Y;Ogawa O;Toguchida J
通讯作者：
Toguchida J
影响因子：
29.4
作者：
Spaderna, Simone;Schmalhofer, Otto;Brabletz, Thomas
通讯作者：
Brabletz, Thomas
microRNA-499-5p通过靶向FOXO4和PDCD4促进结直肠癌细胞侵袭和肿瘤转移
影响因子：
4.7
作者：
Liu, Xiangqiang;Zhang, Zhiyong;Fan, Daiming
通讯作者：
Fan, Daiming
影响因子：
11.2
作者：
Zhang H;Meng F;Liu G;Zhang B;Zhu J;Wu F;Ethier SP;Miller F;Wu G
通讯作者：
Wu G
影响因子：
64.5
作者：
Sykes SM;Lane SW;Bullinger L;Kalaitzidis D;Yusuf R;Saez B;Ferraro F;Mercier F;Singh H;Brumme KM;Acharya SS;Scholl C;Tothova Z;Attar EC;Fröhling S;DePinho RA;Armstrong SA;Gilliland DG;Scadden DT
通讯作者：
Scadden DT