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Cited 42 time in webofscience Cited 43 time in scopus
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Forkhead Transcription Factor FOXO1 Inhibits Angiogenesis in Gastric Cancer in Relation to SIRT1open access

Authors
Kim, SY[Kim, Sue Youn]Ko, YS[Ko, Young San]Park, J[Park, Jinju]Choi, Y[Choi, Yiseul]Park, JW[Park, Jong-Wan]Kim, Y[Kim, Younghoon]Pyo, JS[Pyo, Jung-Soo]Yoo, YB[Yoo, Young Bok]Lee, JS[Lee, Jae-Seon]Lee, BL[Lee, Byung Lan]
Issue Date
Jan-2016
Publisher
KOREAN CANCER ASSOCIATION
Keywords
Stomach neoplasms; Angiogenesis modulating agents; Human FOXO1 protein; Human SIRT1 protein
Citation
CANCER RESEARCH AND TREATMENT, v.48, no.1, pp.345 - 354
Indexed
SCIE
SCOPUS
KCI
Journal Title
CANCER RESEARCH AND TREATMENT
Volume
48
Number
1
Start Page
345
End Page
354
URI
https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/38292
DOI
10.4143/crt.2014.247
ISSN
1598-2998
Abstract
Purpose We previously reported that forkhead transcription factors of the O class 1 (FOXO1) expression in gastric cancer (GC) was associated with angiogenesis-related molecules. However, there is little experimental evidence for the direct role of FOXO1 in GC. In the present study, we investigated the effect of FOXO1 on the tumorigenesis and angiogenesis in GC and its relationship with SIRT1. Materials and Methods Stable GC cell lines (SNU-638 and SNU-601) infected with a lentivirus containing FOXO1 shRNA were established for animal studies as well as cell culture experiments. We used xenograft tumors in nude mice to evaluate the effect of FOXO1 silencing on tumor growth and angiogenesis. In addition, we examined the association between FOXO1 and SIRT1 by immunohistochemical tissue array analysis of 471 human GC specimens and Western blot analysis of xenografted tumor tissues. Results In cell culture, FOXO1 silencing enhanced hypoxia inducible factor-1 alpha (HIF-1 alpha) expression and GC cell growth under hypoxic conditions, but not under normoxic conditions. The xenograft study showed that FOXO1 downregulation enhanced tumor growth, microvessel areas, HIF-1 alpha activation and vascular endothelial growth factor (VEGF) expression. In addition, inactivated FOXO1 expression was associated with SIRT1 expression in human GC tissues and xenograft tumor tissues. Conclusion Our results indicate that FOXO1 inhibits GC growth and angiogenesis under hypoxic conditions via inactivation of the HIF-1 alpha-VEGF pathway, possibly in association with SIRT1. Thus, development of treatment modalities aiming at this pathway might be useful for treating GC.
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