Arginine ADP-ribosyltransferase 1 promotes angiogenesis in colorectal cancer via the PI3K/Akt pathway.

Abstract

Arginine adenosine diphosphate (ADP)-ribosyl-transferase 1 (ART1) is known to play an important role in many physiological and pathological processes. Previous studies have demonstrated that ART1 promotes proliferation, invasion and metastasis in colon carcinoma. However, it was unclear whether ART1 is involved in angiogenesis in cases of colorectal cancer (CRC). In the present study, lentiviral vector‑mediated ART1‑cDNA or ART1-shRNA were transfected into LoVo cells, and the LoVo cells transfected with ART1-cDNA or ART1-shRNA were co-cultured with human umbilical vein endothelial cells (HUVECs) to determine the influence of ART1 on HUVECs. The proliferation, migration and angiogenesis of HUVECs were monitored using a cell counting kit-8 assay, a Transwell migration assay and immunohistochemical analysis in intrasplenic allograft tumors, respectively. Hypoxia‑inducible factor 1-α (HIF-1α), total (t-)Akt, phosphorylated (p-)Akt, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression levels were detected via western blot analysis. Our results revealed that HUVECs which were co-cultured with ART1-cDNA LoVo cells showed higher proliferation, migration and angiogenic abilities, but a reduction was noted in those cultured with ART1-shRNA LoVo cells; p-Akt, HIF-1α, VEGF and bFGF expression was increased in HUVECs cultured with ART1‑cDNA-transfected LoVo cells, but reduced in ART1-shRNA-transfected LoVo cells. In a mouse xenograft model, we noted that the tumor microvessel density (MVD) was significantly increased in intrasplenic transplanted ART1‑cDNA CT26 tumors but decreased in intrasplenic transplanted ART1‑shRNA tumors. These data suggest that ART1 promoted the expression of HIF-1α via the Akt pathway in tumor cells. It also upregulated VEGF and bFGF and enhanced angiogenesis in HUVECs. Thus, we suggest that ART1 plays an important role in the invasion of CRC cells and the metastasis of CRC.

• Authors: Lian Yang, Ming Xiao, Xian Li, Yi Tang, Ya-Lan Wang
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 37 Issue 3 Pg. 734-42 (Mar 2016) ISSN: 1791-244X [Electronic] Greece
• PMID: 26847718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GPI-Linked Proteins
• Hypoxia-Inducible Factor 1, alpha Subunit
• Vascular Endothelial Growth Factor A
• Fibroblast Growth Factor 2
• ADP Ribose Transferases
• ART1 protein, human
• Phosphatidylinositol 3-Kinases
• Oncogene Protein v-akt

Topics

• ADP Ribose Transferases (genetics, metabolism)
• Animals
• Cell Line, Tumor
• Colorectal Neoplasms (genetics, metabolism)
• Female
• Fibroblast Growth Factor 2 (metabolism)
• GPI-Linked Proteins (genetics, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Immunohistochemistry
• Mice
• Neovascularization, Pathologic (metabolism)
• Oncogene Protein v-akt (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Signal Transduction (genetics, physiology)
• Vascular Endothelial Growth Factor A (metabolism)