RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer

Kim,Bo Ram; Kang,Myoung Hee; Kim,Jung Lim; Na,Yoo Jin; Park,Seong Hye; Lee,Sun Il; Kang,Sanghee; Joung,Sung Yup; Lee,Suk-Young; Lee,Dae‑Hee; Min,Byung Wook; Oh,Sang Cheul

doi:10.3892/or.2016.5086

RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer

Authors:
- Bo Ram Kim
- Myoung Hee Kang
- Jung Lim Kim
- Yoo Jin Na
- Seong Hye Park
- Sun Il Lee
- Sanghee Kang
- Sung Yup Joung
- Suk-Young Lee
- Dae‑Hee Lee
- Byung Wook Min
- Sang Cheul Oh
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Affiliations: Graduate School of Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea, University of Ulsan College of Medicine, Asan Institute for Life Science, Seoul 138-736, Republic of Korea, Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 152-703, Republic of Korea
Published online on: September 12, 2016 https://doi.org/10.3892/or.2016.5086
Pages: 2601-2608

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Abstract

Recent studies have determined that inactivation of runt‑related transcription factor 3 (RUNX3) expression is highly associated with lymph node metastasis and poor prognosis in various types of cancer. However, the mechanism of RUNX3-mediated suppression of tumor metastasis remains unclear. Herein, we aimed to clarify the effect of RUNX3 on metastasis and angiogenesis in colorectal cancer (CRC). Firstly, we found that the reduction in expression of RUNX3 in CRC tissues when compared with tumor adjacent normal colon tissues, as indicated by reduced RUNX3 staining, was significantly correlated with tumor-node-metastasis (TNM) stage. Secondly, we demonstrated that RUNX3 overexpression inhibited CRC cell migration and invasion resulting from the upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. In contrast, the knockdown of RUNX3 reduced the inhibition of migration and invasion of CRC cells. Finally, we found that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation in CRC cells. All in all, our findings may provide insight into the development of RUNX3 for CRC metastasis diagnostics and therapeutics.

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