Abstract
The influence of the most important classical mono-ADP-ribosyltransferase, arginine ADP-ribosyltransferase 1 (Art1), on survival and apoptosis of colon carcinoma cells and the potential mechanisms have been partly discussed in our previous study but still need to be further studied. In this present study, Art1 of colon carcinoma CT26 cells was silenced with lentiviral vector-mediated short hairpin RNA (shRNA) or overexpressed with lentiviral vector-mediated complementary DNA (cDNA) and allograft transplant tumors are established in Balb/c mice. We verified Art1 knockdown increases apoptosis of CT26 cells transplant tumor; Art1 overexpression acts oppositely. Accordingly, growth of transplant tumors is inhibited in Art1 knockdown transplant tumors and increases in Art1 overexpression transplant tumors. Furthermore, activity of Akt and Erk cell signal pathways and expression of an apoptosis biomarker, βIII-tubulin (Tubb3), decrease when Art1 was silenced and increase when Art1 was overexpressed. Inhibiting Akt pathway or Erk pathway both downregulates expression of Tubb3 on protein and messenger RNA (mRNA) level, indicating that Tubb3 could be regulated by both Akt and Erk pathways, and plays a role in the influence of Art1 on apoptosis of Balb/c mice allograft transplant tumor. We also demonstrated that Bcl-2 family is not the responsible downstream factor of the Erk pathway in colon carcinoma cells which is undergoing apoptosis. These findings enrich the molecular mechanism for the function of Art1 in colon carcinoma and provide a complementary support for Art1 to be a potential therapeutic target of the treatment of this kind of malignant tumor.
Similar content being viewed by others
References
Braren R, Glowacki G, Nissen M, Haag F, Koch-Nolte F. Molecular characterization and expression of the gene for mouse NAD+:arginine ecto-mono(ADP-ribosyl)transferase, Art1. Biochem J. 1998;336:561–8.
Seman M, Adriouch S, Haag F, Koch-Nolte F. Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling. Curr Med Chem. 2004;11(7):857–72.
Balducci E, Micossi LG, Soldaini E, Rappuoli R. Expression and selective up-regulation of toxin-related mono ADP-ribosyltransferases by pathogen-associated molecular patterns in alveolar epithelial cells. FEBS Lett. 2007;581(22):4199–204.
Del Vecchio M, Balducci E. Mono ADP-ribosylation inhibitors prevent inflammatory cytokine release in alveolar epithelial cells. Mol Cell Biochem. 2008;310(1-2):77–83.
Yang L, Wang YL, Sheng YT, Xiong W, Xu JX, Tang Y, et al. The correlation of ART1 expression with angiogenesis in colorectal carcinoma and it relationship with VEGF and integrin αVβ3 expressions. Basic Clin Med. 2012;32:1064–9.
Xu JX, Wang YL, Tang Y, Xiong W. Effect of ART1 gene silencing by RNA interference on the proliferation of mouse colon carcinoma cells and its possible mechanism. Tumor. 2012;32(12):949–54.
Tang Y, Li M, Wang YL, Threadgill MD, Xiao M, Mou CF, et al. ART1 promotes starvation-induced autophagy: a possible protective role in the development of colon carcinoma. Am J Cancer Res. 2015;5(2):498–513.
Tang Y, Wang YL, Yang L, Xu JX, Xiong W, Xiao M, et al. Inhibition of arginine ADP-ribosyltransferase 1 reduces the expression of poly (ADP-ribose) polymerase-1 in colon carcinoma. Int J Mol Med. 2013;32(1):130.
Xiao M, Tang Y, Wang YL, Yang L, Li X, Kuang J, et al. ART1 silencing enhances apoptosis of mouse CT26 cells via the PI3K/Akt/NF-κB pathway. Cell Physiol Biochem. 2013;32(6):1587–99.
Zolkiewska A, Moss J. Integrin alpha 7 as substrate for a glycosylphosphatidylinositol-anchored ADP-ribosyltransferase on the surface of skeletal muscle cells. J Biol Chem. 1993;268(34):25273–6.
Gilcrease MZ. Integrin signaling in epithelial cells. Cancer Lett. 2007;247(1):1–25.
Liu J, Burkin DJ, Kaufman SJ. Increasing α7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression. Am J Physiol Cell Physiol. 2008;294(2):C627–40.
Levallet G, Bergot E, Antoine M, Creveuil C, Santos AO, Beau-Faller M, et al. High TUBB3 expression, an independent prognostic marker in patients with early non-small cell lung cancer treated by preoperative chemotherapy, is regulated by K-Ras signaling pathway. Mol Cancer Ther. 2012;11(5):1203–13.
Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C. PI3K/Akt and apoptosis: size matters. Oncogene. 2003;22(56):8983–98.
Gan PP, Pasquier E, Kavallaris M. Class III β-tubulin mediates sensitivity to chemotherapeutic drugs in non-small cell lung cancer. Cancer Res. 2007;67(19):9356–63.
Kavallaris M. Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer. 2010;10(3):194–204.
Sève P, Dumontet C. Is class III β-tubulin a predictive factor in patients receiving tubulin-binding agents? Lancet Oncol. 2008;9(2):168–75.
Sève P, Lai R, Ding K, Winton T, Butts C, Mackey J, et al. Class III β-tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of NCIC JBR. 10. Clin Cancer Res. 2007;13(3):994–9.
Mariani M, Shahabi S, Sieber S, Scambia G, Ferlini C. Class III-tubulin (TUBB3): more than a biomarker in solid tumors? Curr Mol Med. 2011;11(9):726–31.
Yoon SO, Kim WY, Go H, Paik JH, Kim JE, Kim YA, et al. Class III beta-tubulin shows unique expression patterns in a variety of neoplastic and non-neoplastic lymphoproliferative disorders. Am J Surg Pathol. 2010;34(5):645–55.
McCarroll JA, Gan PP, Erlich RB, Liu M, Dwarte T, Sagnella S, et al. TUBB3/beta III-tubulin acts through the PTEN/AKT signaling axis to promote tumorigenesis and anoikis resistance in non-small cell lung cancer. Cancer Res. 2015;75(2):415–25.
Gan PP, McCarroll JA, Po’uha ST, Kamath K, Jordan MA, Kavallaris M. Microtubule dynamics, mitotic arrest, and apoptosis: drug-induced differential effects of βIII-tubulin. Mol Cancer Ther. 2010;9(5):1339–48.
Roque DM, Buza N, Glasgow M, Bellone S, Bortolomai I, Gasparrini S, et al. Class III beta-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel. Clin Exp Metastasis. 2014;31(1):101–10.
Tsourlakis MC, Weigand P, Grupp K, Kluth M, Steurer S, Schlomm T, et al. betaIII-Tubulin overexpression is an independent predictor of prostate cancer progression tightly linked to ERG fusion status and PTEN deletion. Am J Pathol. 2014;184(3):609–17.
Urano N, Fujiwara Y, Doki Y, Kim SJ, Miyoshi Y, Noguchi S, et al. Clinical significance of class III beta-tubulin expression and its predictive value for resistance to docetaxel-based chemotherapy in gastric cancer. Int J Oncol. 2006;28(2):375–81.
Yu J, Gao J, Lu Z, Gong J, Li Y, Dong B, et al. Combination of microtubule associated protein-tau and β-tubulin III predicts chemosensitivity of paclitaxel in patients with advanced gastric cancer. Eur J Cancer. 2004;50(13):2328–35.
Mariani M, Zannoni GF, Sioletic S, Sieber S, Martino C, Martinelli E, et al. Gender influences the class III and V beta-tubulin ability to predict poor outcome in colorectal cancer. Clin Cancer Res. 2012;18(10):2964–75.
Kuang J, Wang YL, Xiao M, Tang Y, Chen WW, Song GL, et al. Synergistic effect of arginine-specific ADP-ribosyltransferase 1 and poly(ADP-ribose) polymerase-1 on apoptosis induced by cisplatin in CT26 cells. Oncol Rep. 2014;31(5):2335–43.
O’Dwyer PJ, Moyer JD, Suffness M, Harrison SD, Cysyk R, Hamilton TC, et al. Antitumor activity and biochemical effects of aphidicolin glycinate (NSC 303812) alone and in combination with cisplatin in vivo. Cancer Res. 1994;54(3):724–9.
Lee CK, Park KK, Lim SS, Park JHY, Chung WY. Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer. Biol Pharm Bull. 2007;30(11):2191–5.
Carlsson G, Gullberg B, Hafström L. Estimation of liver tumor volume using different formulas—an experimental study in rats. J Cancer Res Clin Oncol. 1983;105(1):20–3.
Vlahos CJ, Matter WF, Hui KY, Brown RF. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem. 1994;269(7):5241–8.
Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem. 1995;270(46):27489–94.
Soldani C, Scovassi A. Poly (ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis. 2002;7(4):321–8.
Peralta-Leal A, Rodríguez-Vargas JM, Aguilar-Quesada R, Rodríguez MI, Linares JL, de Almodóvar MR, et al. PARP inhibitors: new partners in the therapy of cancer and inflammatory diseases. Free Radic Biol Med. 2009;47:13–26.
Galluzzi L, Vitale I, Abrams JM, et al. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 2012;19:107–2.
Langelier MF, Pascal JM. PARP-1 mechanism for coupling DNA damage detection to poly(ADP-ribose) synthesis. Curr Opin Struct Biol. 2013;23:134–43.
Kavallaris M, Kuo DY, Burkhart CA, Regl DL, Norris MD, Haber M, et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Investig. 1997;100(5):1282–93.
Seve P, Mackey J, Isaac S, Tredan O, Souquet PJ, Perol M, et al. Class III beta-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel. Mol Cancer Ther. 2005;4(12):2001–7.
Ferrandina G, Zannoni GF, Martinelli E, Paglia A, Gallotta V, Mozzetti S, et al. Class III β-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin Cancer Res. 2006;12(9):2774–9.
Mozzetti S, Ferlini C, Concolino P, Filippetti F, Raspaglio G, Prislei S, et al. Class III β-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res. 2005;11(1):298–305.
Derry WB, Wilson L, Khan IA, Luduena RF, Jordan MA. Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified beta-tubulin isotypes. Biochemistry. 1997;36(12):3554–62.
Raspaglio G, Filippetti F, Prislei S, Penci R, De Maria I, Cicchillitti L, et al. Hypoxia induces class III beta-tubulin gene expression by HIF-1α binding to its 3′ flanking region. Gene. 2008;409(1):100–8.
Powell S, Kaizer A, Koopmeiners JS, Iwamoto C, Klein M. High expression of class III β-tubulin in small cell lung carcinoma. Oncol Lett. 2014;7(2):405–10.
Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721–32.
Carre M, Carles G, Andre N, Douillard S, Ciccolini J, Briand C, et al. Involvement of microtubules and mitochondria in the antagonism of arsenic trioxide on paclitaxel-induced apoptosis. Biochem Pharmacol. 2002;63(10):1831–42.
Mollinedo F, Gajate C. Microtubules, microtubule-interfering agents and apoptosis. Apoptosis. 2003;8(5):413–50.
Carré M, André N, Carles G, Borghi H, Brichese L, Briand C, et al. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J Biol Chem. 2002;277(37):33664–9.
Rostovtseva TK, Sheldon KL, Hassanzadeh E, Monge C, Saks V, Bezrukov SM, et al. Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration. Proc Natl Acad Sci U S A. 2008;105(48):18746–51.
Tsujimoto Y. Bcl-2 family of proteins: life-or-death switch in mitochondria. Biosci Rep. 2002;22(1):47–58.
Shimizu S, Matsuoka Y, Shinohara Y, Yoneda Y, Tsujimoto Y. Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells. J Cell Biol. 2001;152(2):237–50.
Zhao Z, Gruszczynska-Biegala J, Zolkiewska A. ADP-ribosylation of integrin alpha7 modulates the binding of integrin alpha7beta1 to laminin. Biochem J. 2005;385(Pt 1):309–17.
Acknowledgments
This research was supported by Project Supported by Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJ110322) and the Ministry of Education Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20105503110009).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
None
Rights and permissions
About this article
Cite this article
Xiao, M., Tang, Y., Chen, WW. et al. Tubb3 regulation by the Erk and Akt signaling pathways: a mechanism involved in the effect of arginine ADP-ribosyltransferase 1 (Art1) on apoptosis of colon carcinoma CT26 cells. Tumor Biol. 37, 2353–2363 (2016). https://doi.org/10.1007/s13277-015-4058-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-4058-y