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

Yang,Lian; Xiao,Ming; Li,Xian; Tang,Yi; Wang,Ya-Lan

doi:10.3892/ijmm.2016.2473

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

Authors:
- Lian Yang
- Ming Xiao
- Xian Li
- Yi Tang
- Ya-Lan Wang
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Affiliations: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: January 29, 2016 https://doi.org/10.3892/ijmm.2016.2473
Pages: 734-742
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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1	Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z and Hanahan D: Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2:737–744. 2000. View Article : Google Scholar : PubMed/NCBI
2	Seman M, Adriouch S, Haag F and Koch-Nolte F: Ecto-ADP-ribosyltransferases (ARTs): Emerging actors in cell communication and signaling. Curr Med Chem. 11:857–872. 2004. View Article : Google Scholar : PubMed/NCBI
3	Braren R, Glowacki G, Nissen M, Haag F and Koch-Nolte F: Molecular characterization and expression of the gene for mouse NAD⁺: arginine ecto-mono(ADP-ribosyl)transferase, Art1. Biochem J. 336:561–568. 1998. View Article : Google Scholar
4	Corda D and Di Girolamo M: Functional aspects of protein mono-ADP-ribosylation. EMBO J. 22:1953–1958. 2003. View Article : Google Scholar : PubMed/NCBI
5	Okazaki IJ, Zolkiewska A, Nightingale MS and Moss J: Immunological and structural conservation of mammalian skeletal muscle glycosylphosphatidylinositol-linked ADP-ribosyltransferases. Biochemistry. 33:12828–12836. 1994. View Article : Google Scholar : PubMed/NCBI
6	Kefalas P, Allport JR, Donnelly LE, Rendell NB, Murray S, Taylor GW, Lo G, Yadollahi-Farsani M and MacDermot J: Arginine-specific mono(ADP-ribosyl)transferase activity in human neutrophil polymorphs. A possible link with the assembly of filamentous actin and chemotaxis. Adv Exp Med Biol. 419:241–244. 1997. View Article : Google Scholar : PubMed/NCBI
7	Balducci E, Horiba K, Usuki J, Park M, Ferrans VJ and Moss J: Selective expression of RT6 superfamily in human bronchial epithelial cells. Am J Respir Cell Mol Biol. 21:337–346. 1999. View Article : Google Scholar : PubMed/NCBI
8	Zolkiewska A and Moss J: Integrin alpha 7 as substrate for a glycosylphosphatidylinositol-anchored ADP-ribosyltransferase on the surface of skeletal muscle cells. J Biol Chem. 268:25273–25276. 1993.PubMed/NCBI
9	Nemoto E, Yu Y and Dennert G: Cell surface ADP-ribosyltransferase regulates lymphocyte function-associated molecule-1 (LFA-1) function in T cells. J Immunol. 157:3341–3349. 1996.PubMed/NCBI
10	Wang J, Nemoto E and Dennert G: Regulation of CTL by ecto-nictinamide adenine dinucleotide (NAD) involves ADP-ribosylation of a p56lck-associated protein. J Immunol. 156:2819–2827. 1996.PubMed/NCBI
11	Laing S, Unger M, Koch-Nolte F and Haag F: ADP-ribosylation of arginine. Amino Acids. 41:257–269. 2011. View Article : Google Scholar :
12	Saxty BA, Yadollahi-Farsani M, Upton PD, Johnstone SR and MacDermot J: Inactivation of platelet-derived growth factor-BB following modification by ADP-ribosyltransferase. Br J Pharmacol. 133:1219–1226. 2001. View Article : Google Scholar : PubMed/NCBI
13	Kato J, Zhu J, Liu C and Moss J: Enhanced sensitivity to cholera toxin in ADP-ribosylarginine hydrolase-deficient mice. Mol Cell Biol. 27:5534–5543. 2007. View Article : Google Scholar : PubMed/NCBI
14	Del Vecchio M and Balducci E: Mono ADP-ribosylation inhibitors prevent inflammatory cytokine release in alveolar epithelial cells. Mol Cell Biochem. 310:77–83. 2008. View Article : Google Scholar
15	Stevens LA, Levine RL, Gochuico BR and Moss J: ADP-ribosylation of human defensin HNP-1 results in the replacement of the modified arginine with the noncoded amino acid ornithine. Proc Natl Acad Sci USA. 106:19796–19800. 2009. View Article : Google Scholar : PubMed/NCBI
16	Liu ZX, Yu Y and Dennert G: A cell surface ADP-ribosyltransferase modulates T cell receptor association and signaling. J Biol Chem. 274:17399–17401. 1999. View Article : Google Scholar : PubMed/NCBI
17	Akai T, Nabeya Y, Yahiro K, Morinaga N, Mitsuhashi K, Inoue M, Sakamoto A, Ochiai T and Noda M: Helicobacter pylori induces mono-(adenosine 5′-diphosphate)-ribosylation in human gastric adenocarcinoma. Int J Oncol. 29:965–972. 2006.PubMed/NCBI
18	Balducci E, Micossi LG, Soldaini E and Rappuoli R: Expression and selective up-regulation of toxin-related mono ADP-ribosyltransferases by pathogen-associated molecular patterns in alveolar epithelial cells. FEBS Lett. 581:4199–4204. 2007. View Article : Google Scholar : PubMed/NCBI
19	Yang L, Wang YL, Sheng YT, Xiong W, Xu JX, Tang Y and Li X: The correlation of ART1 expression with angiogenesis in colorectal carcinoma and its relationship with VEGF and integrin αVβ3 expressions. J Basic Clin Med. 32:1065–1069. 2012.
20	Fang J, Ding M, Yang L, Liu LZ and Jiang BH: PI3K/PTEN/AKT signaling regulates prostate tumor angiogenesis. Cell Signal. 19:2487–2497. 2007. View Article : Google Scholar : PubMed/NCBI
21	Gray MJ, Zhang J, Ellis LM, Semenza GL, Evans DB, Watowich SS and Gallick GE: HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Oncongene. 24:3110–3120. 2005. View Article : Google Scholar
22	Tang Y, Wang Y-L, Yang L, Xu J-X, Xiong W, Xiao M and Li M: Inhibition of arginine ADP-ribosyltransferase 1 reduces the expression of poly(ADP-ribose) polymerase-1 in colon carcinoma. Int J Mol Med. 32:130–136. 2013.PubMed/NCBI
23	Yang LP, Cheng P, Peng XC, Shi HS, He WH, Cui FY, Luo ST, Wei YQ and Yang L: Anti-tumor effect of adenovirus-mediated gene transfer of pigment epithelium-derived factor on mouse B16-F10 melanoma. J Exp Clin Cancer Res. 28:75–78. 2009. View Article : Google Scholar : PubMed/NCBI
24	Huang C, Yuan X, Li Z, Tian Z, Zhan X, Zhang J and Li X: VE-statin/Egfl7 siRNA inhibits angiogenesis in malignant glioma in vitro. Int J Clin Exp Pathol. 7:1077–1084. 2014.PubMed/NCBI
25	Rajesh M, Mukhopadhyay P, Godlewski G, Bátkai S, Haskó G, Liaudet L and Pacher P: Poly(ADP-ribose)polymerase inhibition decreases angiogenesis. Biochem Biophys Res Commun. 350:1056–1062. 2006. View Article : Google Scholar : PubMed/NCBI
26	Neo JH, Malcontenti-Wilson C, Muralidharan V and Christophi C: Effect of ACE inhibitors and angiotensin II receptor antagonists in a mouse model of colorectal cancer liver metastases. J Gastroenterol Hepatol. 22:577–584. 2007. View Article : Google Scholar : PubMed/NCBI
27	Weidner N, Semple JP, Welch WR and Folkman J: Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma. N Engl J Med. 324:1–8. 1991. View Article : Google Scholar : PubMed/NCBI
28	Xiao M, Tang Y, Wang YL, Yang L, Li X, Kuang J and Song GL: ART1 silencing enhances apoptosis of mouse CT26 cells via the PI3K/Akt/NF-κB pathway. Cell Physiol Biochem. 32:1587–1599. 2013.
29	Xu JX, Wang YL, Tang Y and Xiong W: RNA interference of ART1 on colon cancer cell proliferation in mice and its mechanism. Tumor. 32:949–954. 2012.
30	Wei X, Tang Y, Wang Y and Xu J-X: Effects of ART1 gene silencing on the ability of CT26 cellular matrix adhesion and migration. Fudan Univ J Med Sci. 40:328–334. 2013.
31	Imura S, Miyake H, Izumi K, Tashiro S and Uehara H: Correlation of vascular endothelial cell proliferation with microvessel density and expression of vascular endothelial growth factor and basic fibroblast growth factor in hepatocellular carcinoma. J Med Invest. 51:202–209. 2004. View Article : Google Scholar : PubMed/NCBI
32	Raspollini MR, Castiglione F, Garbini F, Villanucci A, Amunni G, Baroni G, Boddi V and Taddei GL: Correlation of epidermal growth factor receptor expression with tumor microdensity vessels and with vascular endothelial growth factor expression in ovarian carcinoma. Int J Surg Pathol. 13:135–142. 2005. View Article : Google Scholar : PubMed/NCBI
33	Eriksson K, Magnusson P, Dixelius J, Claesson-Welsh L and Cross MJ: Angiostatin and endostatin inhibit endothelial cell migration in response to FGF and VEGF without interfering with specific intracellular signal transduction pathways. FEBS Lett. 536:192242003. View Article : Google Scholar
34	Su Y, Guan XQ, Liu FQ and Wang YL: The effects of MIBG on the invasive properties of HepG2 hepatocellular carcinoma cells. Int J Mol Med. 34:842–848. 2014.PubMed/NCBI
35	Bondarenko VA and Yamazaki A: Characterization of argininespecific mono-ADP ribosyltransferase isolated from frog retina and its function in signal transduction. Invest Ophthalmol Vis Sci. 50:5440–A391. 2009.
36	Kerbel RS: Tumor angiogenesis. N Engl J Med. 358:2039–2049. 2008. View Article : Google Scholar : PubMed/NCBI
37	McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Montalto G, Cervello M, Nicoletti F, Fagone P, Malaponte G, Mazzarino MC, et al: Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget. 3:954–987. 2012. View Article : Google Scholar : PubMed/NCBI
38	Hart JR and Vogt PK: Phosphorylation of AKT: a mutational analysis. Oncotarget. 2:467–476. 2011. View Article : Google Scholar : PubMed/NCBI
39	Sheng S, Qiao M and Pardee AB: Metastasis and AKT activation. J Cell Physiol. 218:451–454. 2009. View Article : Google Scholar
40	Hawkins PT, Anderson KE, Davidson K and Stephens LR: Signalling through class I PI3Ks in mammalian cells. Biochem Soc Trans. 34:647–662. 2006. View Article : Google Scholar : PubMed/NCBI
41	Agani F and Jiang BH: Oxygen-independent regulation of HIF-1: novel involvement of PI3K/AKT/mTOR pathway in cancer. Curr Cancer Drug Targets. 13:245–251. 2013. View Article : Google Scholar : PubMed/NCBI
42	Semenza GL: HIF-1: Upstream and downstream of cancer metabolism. Curr Opin Genet Dev. 20:51–56. 2010. View Article : Google Scholar :
43	Lu X and Kang Y: Hypoxia and hypoxia-inducible factors: master regulators of metastasis. Clin Cancer Res. 16:5928–5935. 2010. View Article : Google Scholar : PubMed/NCBI
44	Rohwer N and Cramer T: HIFs as central regulators of gastric cancer pathogenesis. Cancer Biol Ther. 10:383–385. 2010. View Article : Google Scholar : PubMed/NCBI
45	Kitajima Y and Miyazaki K: The critical impact of HIF-1α on gastric cancer biology. Cancers (Basel). 5:15–26. 2013. View Article : Google Scholar
46	Lee BL, Kim WH, Jung J, Cho SJ, Park JW, Kim J, Chung HY, Chang MS and Nam SY: A hypoxia-independent up-regulation of hypoxia-inducible factor-1 by AKT contributes to angiogenesis in human gastric cancer. Carcinogenesis. 29:44–51. 2008. View Article : Google Scholar
47	Chun SY, Johnson C, Washburn JG, Cruz-Correa MR, Dang DT and Dang LH: Oncogenic KRAS modulates mitochondrial metabolism in human colon cancer cells by inducing HIF-1α and HIF-2α target genes. Mol Cancer. 9:2932010. View Article : Google Scholar
48	Pugh CW and Ratcliffe PJ: Regulation of angiogenesis by hypoxia-inducible factor-1: role of the HIF system. Nat Med. 9:677–684. 2003. View Article : Google Scholar : PubMed/NCBI
49	Lang SA, Gaumann A, Koehl GE, Seidel U, Bataille F, Klein D, Ellis LM, Bolder U, Hofstaedter F, Schlitt HJ, et al: Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer. 120:1803–1810. 2007. View Article : Google Scholar : PubMed/NCBI