39. Ribeiro-Filho LA, Franks J, Sasaki M, Shiina H, Li LC, et al. (2002) CpG hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer. Mol Carcinog 34: 187–198. 40. Conacci-Sorrell M, Zhurinsky J, Ben-Ze’ev A (2002) The cadherin-catenin adhesion system in signaling and cancer. J Clin Invest 109: 987–991. 41. Birchmeier W, Behrens J (1994) Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1198: 11–26. 42. Rieger KM, Little AF, Swart JM, Kastrinakis WV, Fitzgerald JM, et al. (1995) Human bladder carcinoma cell lines as indicators of oncogenic change relevant to urothelial neoplastic progression. Br J Cancer 72: 683–690. 43. Yates DR, Rehman I, Abbod MF, Meuth M, Cross SS, et al. (2007) Promoter hypermethylation identifies progression risk in bladder cancer. Clin Cancer Res 13: 2046–2053. 44. Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, et al. (1991) E-cadherin- mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol 113: 173–185. 45. Vleminckx K, Vakaet L, Jr., Mareel M, Fiers W, van Roy F (1991) Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 66: 107–119. 46. Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G (1998) A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392: 190–193. 47. Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1: 46–54. 48. Black PC, Brown GA, Inamoto T, Shrader M, Arora A, et al. (2008) Sensitivity to epidermal growth factor receptor inhibitor requires E-cadherin expression in urothelial carcinoma cells. Clin Cancer Res 14: 1478–1486. E-Cadherin Growth Regulation 49. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, et al. (2008) Loss of E- cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res 68: 3645–3654. 50. Bornman DM, Mathew S, Alsruhe J, Herman JG, Gabrielson E (2001) Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial epithelium from elderly individuals. Am J Pathol 159: 831–835. 51. Fadare O, Reddy H, Wang J, Hileeto D, Schwartz PE, et al. (2005) E-Cadherin and beta-Catenin expression in early stage cervical carcinoma: a tissue microarray study of 147 cases. World J Surg Oncol 3: 38. 52. Moll R, Mitze M, Frixen UH, Birchmeier W (1993) Differential loss of E- cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 143: 1731–1742. 53. Shaw NJ, Georgopoulos NT, Southgate J, Trejdosiewicz LK (2005) Effects of loss of p53 and p16 function on life span and survival of human urothelial cells. Int J Cancer 116: 634–639. 54. Georgopoulos NT, Steele LP, Thomson MJ, Selby PJ, Southgate J, et al. (2006) A novel mechanism of CD40-induced apoptosis of carcinoma cells involving TRAF3 and JNK/AP-1 activation. Cell Death Differ 13: 1789–1801. 55. Georgopoulos NT, Merrick A, Scott N, Selby PJ, Melcher A, et al. (2007) CD40- mediated death and cytokine secretion in colorectal cancer: a potential target for inflammatory tumour cell killing. Int J Cancer 121: 1373–1381. 56. Chopra B, Georgopoulos NT, Nicholl A, Hinley J, Oleksiewicz MB, et al. (2009) Structurally diverse peroxisome proliferator-activated receptor agonists induce apoptosis in human uro-epithelial cells by a receptor-independent mechanism involving store-operated calcium channels. Cell Prolif 42: 688–700. PLoS ONE | www.plosone.org 12 October 2010 | Volume 5 | Issue 10 | e13621