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Abstract
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.
Highlights
Forkhead box O4 (FOXO4), a member of the forkhead box class O (FOXO) family of transcription factors, is currently the focus of intense study
Expression of FOXO4 is down-regulated in GC tissues and cell lines To examine whether the FOXO4 expression was altered in GC, the expression and subcellular localization of FOXO4 were studied in a tissue microarray of 75 paired GC samples by using an immunohistochemical assay
The FOXO4 staining in nontumorous tissues (NT) was consistently stronger than that of the GC samples, and there was a significant difference between the staining results of the GC and NT samples (Figure 1A2) (P < 0.05)
Summary
FOXO4, 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. The FOXO transcription factors family comprises four highly related members: FOXO1, FOXO3, FOXO4, and FOXO6 [6,7,8]. The expression and function of FOXO4 in gastric cancer were not known yet. The aim of our work has been to investigate the possible role of FOXO4 in gastric cancer carcinogenesis. We report that FOXO4 repress cell proliferation and metastasis in gastric cancer by the regulation G1 cellcycle arrest and vimentin
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