title: RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer.
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.
authors.affiliation: Graduate School of Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Kim
authors.affiliation: University of Ulsan College of Medicine, Asan Institute for Life Science, Seoul 138-736, Republic of Korea.
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kang
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Jung Lim
authors.initials: JL
authors.lastname: Kim
authors.affiliation: Graduate School of Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Na
authors.affiliation: Graduate School of Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Seong Hye
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Sun Il
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Sung Yup
authors.initials: SY
authors.lastname: Joung
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Suk-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Graduate School of Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Byung Wook
authors.initials: BW
authors.lastname: Min
authors.affiliation: Graduate School of Medicine, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Sang Cheul
authors.initials: SC
authors.lastname: Oh
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9