1 Wang YH, Yeh SD, Shen KH, Shen CH, Juang GD, Hsu LI et al. A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma. Toxicol Appl Pharmacol 2009; 241: 111–118.

2 Roupret M, Zigeuner R, Palou J, Boehle A, Kaasinen E, Sylvester R et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol 2011; 59: 584–594.

3 Studer UE, Bacchi M, Biedermann C, Jaeger P, Kraft R, Mazzucchelli L et al. Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial. J Urol 1994; 152: 81–84.

4 Kakizoe T . Development and progression of urothelial carcinoma. Cancer Sci 2006; 97: 821–828.

5 Kim WJ, Bae SC . Molecular biomarkers in urothelial bladder cancer. Cancer Sci 2008; 99: 646–652.

6 Costa VL, Henrique R, Ribeiro FR, Carvalho JR, Oliveira J, Lobo F et al. Epigenetic regulation of Wnt signaling pathway in urological cancer. Epigenetics 2010; 5: 343–351.

7 Kastritis E, Murray S, Kyriakou F, Horti M, Tamvakis N, Kavantzas N et al. Somatic mutations of adenomatous polyposis coli gene and nuclear b-catenin accumulation have prognostic significance in invasive urothelial carcinomas: evidence for Wnt pathway implication. Int J Cancer 2009; 124: 103–108.

8 Schulz WA . Understanding urothelial carcinoma through cancer pathways. Int J Cancer 2006; 119: 1513–1518.

9 Shiina H, Igawa M, Shigeno K, Terashima M, Deguchi M, Yamanaka M et al. Beta-catenin mutations correlate with over expression of C-myc and cyclin D1 genes in bladder cancer. J Urol 2002; 168: 2220–2226.

10 Urakami S, Shiina H, Enokida H, Kawakami T, Tokizane T, Ogishima T et al. Epigenetic inactivation of Wnt inhibitory factor-1 plays an important role in bladder cancer through aberrant canonical Wnt/beta-catenin signaling pathway. Clin Cancer Res 2006; 12: 383–391.

11 Vander Heiden MG, Cantley LC, Thompson CB . Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324: 1029–1033.

12 Levine AJ, Puzio-Kuter AM . The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 2010; 330: 1340–1344.

13 Cairns RA, Harris IS, Mak TW . Regulation of cancer cell metabolism. Nat Rev Cancer 2011; 11: 85–95.

14 Koppenol WH, Bounds PL, Dang CV . Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011; 11: 325–337.

15 Khandekar MJ, Cohen P, Spiegelman BM . Molecular mechanisms of cancer development in obesity. Nat Rev Cancer 2011; 11: 886–895.

16 Kersten S . Regulation of lipid metabolism via angiopoietin-like proteins. Biochem Soc Trans 2005; 33: 1059–1062.

17 Oike Y, Akao M, Kubota Y, Suda T . Angiopoietin-like proteins: potential new targets for metabolic syndrome therapy. Trends Mol Med 2005; 11: 473–479.

18 Ge H, Yang G, Huang L, Motola DL, Pourbahrami T, Li C . Oligomerization and regulated proteolytic processing of angiopoietin-like protein 4. J Biol Chem 2004; 279: 2038–2045.

19 Hato T, Tabata M, Oike Y . The role of angiopoietin-like proteins in angiogenesis and metabolism. Trends Cardiovasc Med 2008; 18: 6–14.

20 Katoh Y, Katoh M . Comparative integromics on angiopoietin family members. Int J Mol Med 2006; 17: 1145–1149.

21 Kim I, Kim HG, Kim H, Kim HH, Park SK, Uhm CS et al. Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis. Biochem J 2000; 346 (Pt 3): 603–610.

22 Kim SH, Park YY, Kim SW, Lee JS, Wang D, DuBois RN . ANGPTL4 induction by prostaglandin E2 under hypoxic conditions promotes colorectal cancer progression. Cancer Res 2011; 71: 7010–7020.

23 Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR et al. TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 2008; 133: 66–77.

24 Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A et al. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol Cell Biol 2000; 20: 5343–5349.

25 Zhu P, Tan MJ, Huang RL, Tan CK, Chong HC, Pal M et al. Angiopoietin-like 4 protein elevates the prosurvival intracellular O2(-):H2O2 ratio and confers anoikis resistance to tumors. Cancer Cell 2011; 19: 401–415.

26 Chomel C, Cazes A, Faye C, Bignon M, Gomez E, Ardidie-Robouant C et al. Interaction of the coiled-coil domain with glycosaminoglycans protects angiopoietin-like 4 from proteolysis and regulates its antiangiogenic activity. FASEB J 2009; 23: 940–949.

27 Lei X, Shi F, Basu D, Huq A, Routhier S, Day R et al. Proteolytic processing of angiopoietin-like protein 4 by proprotein convertases modulates its inhibitory effects on lipoprotein lipase activity. J Biol Chem 2011; 286: 15747–15756.

28 Yang YH, Wang Y, Lam KS, Yau MH, Cheng KK, Zhang J et al. Suppression of the Raf/MEK/ERK signaling cascade and inhibition of angiogenesis by the carboxyl terminus of angiopoietin-like protein 4. Arterioscler Thromb Vasc Biol 2008; 28: 835–840.

29 Cazes A, Galaup A, Chomel C, Bignon M, Brechot N, Le Jan S et al. Extracellular matrix-bound angiopoietin-like 4 inhibits endothelial cell adhesion, migration, and sprouting and alters actin cytoskeleton. Circ Res 2006; 99: 1207–1215.

30 Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L et al. Angiopoietin-like 4 interacts with integrins beta1 and beta5 to modulate keratinocyte migration. Am J Pathol 2010; 177: 2791–2803.

31 Huang RL, Teo Z, Chong HC, Zhu P, Tan MJ, Tan CK et al. ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters. Blood 2011; 118: 3990–4002.

32 Nakayama T, Hirakawa H, Shibata K, Nazneen A, Abe K, Nagayasu T et al. Expression of angiopoietin-like 4 (ANGPTL4) in human colorectal cancer: ANGPTL4 promotes venous invasion and distant metastasis. Oncol Rep 2011; 25: 929–935.

33 Zhang H, Wong CC, Wei H, Gilkes DM, Korangath P, Chaturvedi P et al. HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs. Oncogene 2012; 31: 1757–1770.

34 Feng S, Agoulnik IU, Truong A, Li Z, Creighton CJ, Kaftanovskaya EM et al. Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis. Endocr Relat Cancer 2010; 17: 1021–1033.

35 Shibata K, Nakayama T, Hirakawa H, Hidaka S, Nagayasu T . Clinicopathological significance of angiopoietin-like protein 4 expression in oesophageal squamous cell carcinoma. J Clin Pathol 2010; 63: 1054–1058.

36 Wang Z, Han B, Zhang Z, Pan J, Xia H . Expression of angiopoietin-like 4 and tenascin C but not cathepsin C mRNA predicts prognosis of oral tongue squamous cell carcinoma. Biomarkers 2010; 15: 39–46.

37 Hu J, Jham BC, Ma T, Friedman ER, Ferreira L, Wright JM et al. Angiopoietin-like 4: a novel molecular hallmark in oral Kaposi's sarcoma. Oral Oncol 2011; 47: 371–375.

38 Hattori N, Okochi-Takada E, Kikuyama M, Wakabayashi M, Yamashita S, Ushijima T . Methylation silencing of angiopoietin-like 4 in rat and human mammary carcinomas. Cancer Sci 2011; 102: 1337–1343.

39 Kaneda A, Kaminishi M, Yanagihara K, Sugimura T, Ushijima T . Identification of silencing of nine genes in human gastric cancers. Cancer Res 2002; 62: 6645–6650.

40 Zhang H, Wei S, Ning S, Jie Y, Ru Y, Gu Y . Evaluation of TGFbeta, XPO4, elF5A2 and ANGPTL4 as biomarkers in HCC. Exp Ther Med 2013; 5: 119–127.

41 Verine J, Lehmann-Che J, Soliman H, Feugeas JP, Vidal JS, Mongiat-Artus P et al. Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma. PLoS ONE 2010; 5: e10421.

42 Nakayama T, Hirakawa H, Shibata K, Abe K, Nagayasu T, Taguchi T . Expression of angiopoietin-like 4 in human gastric cancer: ANGPTL4 promotes venous invasion. Oncol Rep 2010; 24: 599–606.

43 Ito Y, Oike Y, Yasunaga K, Hamada K, Miyata K, Matsumoto S et al. Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4. Cancer Res 2003; 63: 6651–6657.

44 Okochi-Takada E, Hattori N, Tsukamoto T, Miyamoto K, Ando T, Ito S et al. ANGPTL4 is a secreted tumor suppressor that inhibits angiogenesis. Oncogene 2014; 33: 2273–2278.

45 Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L et al. Angiopoietin-like 4 interacts with matrix proteins to modulate wound healing. J Biol Chem 2010; 285: 32999–33009.

46 Arnold SA, Brekken RA . SPARC: a matricellular regulator of tumorigenesis. J Cell Commun Signal 2009; 3: 255–273.

47 Chiodoni C, Colombo MP, Sangaletti S . Matricellular proteins: from homeostasis to inflammation, cancer, and metastasis. Cancer Metastasis Rev 2010; 29: 295–307.

48 Galaup A, Cazes A, Le Jan S, Philippe J, Connault E, Le Coz E et al. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci USA 2006; 103: 18721–18726.

49 Hsieh HY, Shen CH, Lin RI, Feng YM, Huang SY, Wang YH et al. Cyproheptadine exhibits antitumor activity in urothelial carcinoma cells by targeting GSK3beta to suppress mTOR and beta-catenin signaling pathways. Cancer Lett 2016; 370: 56–65.

50 Muendlein A, Saely CH, Leiherer A, Fraunberger P, Kinz E, Rein P et al. Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients. Atherosclerosis 2014; 237: 632–638.

51 Wu YQ, Shen YC, Wang H, Zhang JL, Li DD, Zhang X et al. Serum angiopoietin-like 4 is over-expressed in COPD patients: association with pulmonary function and inflammation. Eur Rev Med Pharmacol Sci 2016; 20: 44–53.

52 Swales C, Athanasou NA, Knowles HJ . Angiopoietin-like 4 is over-expressed in rheumatoid arthritis patients: association with pathological bone resorption. PLoS ONE 2014; 9: e109524.

53 Clement LC, Mace C, Avila-Casado C, Joles JA, Kersten S, Chugh SS . Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome. Nat Med 2014; 20: 37–46.

54 Tjeerdema N, Georgiadi A, Jonker JT, van Glabbeek M, Alizadeh Dehnavi R, Tamsma JT et al. Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes. BMJ Open Diabetes Res Care 2014; 2: e000034.

55 Chong HC, Tan CK, Huang RL, Tan NS . Matricellular proteins: a sticky affair with cancers. J Oncol 2012; 2012: 351089.

56 Tan MJ, Teo Z, Sng MK, Zhu P, Tan NS . Emerging roles of angiopoietin-like 4 in human cancer. Mol Cancer Res 2012; 10: 677–688.

57 Huang C, Jacobson K, Schaller MD . MAP kinases and cell migration. J Cell Sci 2004; 117: 4619–4628.

58 Foreman JE, Sharma AK, Amin S, Gonzalez FJ, Peters JM . Ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) inhibits cell growth in a mouse mammary gland cancer cell line. Cancer Lett 2010; 288: 219–225.

59 Girroir EE, Hollingshead HE, Billin AN, Willson TM, Robertson GP, Sharma AK et al. Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines. Toxicology 2008; 243: 236–243.

60 Ng KT, Xu A, Cheng Q, Guo DY, Lim ZX, Sun CK et al. Clinical relevance and therapeutic potential of angiopoietin-like protein 4 in hepatocellular carcinoma. Mol Cancer 2014; 13: 196.

61 Yeh CM, Shay J, Zeng TC, Chou JL, Huang TH, Lai HC et al. Epigenetic silencing of ARNTL, a circadian gene and potential tumor suppressor in ovarian cancer. Int J Oncol 2014; 45: 2101–2107.

62 Ma T, Jham BC, Hu J, Friedman ER, Basile JR, Molinolo A et al. Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi's sarcoma. Proc Natl Acad Sci USA 2010; 107: 14363–14368.

63 Pasin E, Josephson DY, Mitra AP, Cote RJ, Stein JP . Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history. Rev Urol 2008; 10: 31–43.

64 Wang YH, Chiou HY, Lin CT, Hsieh HY, Wu CC, Hsu CD et al. Association between survivin gene promoter -31 C/G polymorphism and urothelial carcinoma risk in Taiwanese population. Urology 2009; 73: 670–674.

65 Lin HY, Hung SK, Lee MS, Chiou WY, Huang TT, Tseng CE et al. DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study. Oncotarget 2015; 6: 915–934.

66 Zordan MD, Mill CP, Riese DJ 2nd, Leary JF . A high throughput, interactive imaging, bright-field wound healing assay. Cytometry A 2011; 79: 227–232.

67 Huang, da W, Sherman BT, Lempicki RA . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4: 44–57.