Cancer Epgienetics / Tumor Virology Lab
| Address: | Rm 315, Sir YK Pao Cancer Centre Department of Clinical Oncology Prince of Wales Hospital The Chinese University of Hong Kong |
| Tel: | (852) 3505-1340/1126 |
| Fax: | (852) 2648-8842 |
| Principal Investigator: | Qian Tao, Ph.D. Professor |
| E-mail: | qtao@clo.cuhk.edu.hk |
| Tel: | (852) 3505-1340 |
| Link: | https://www.lihs.cuhk.edu.hk/en-us/research/investigators/taoqian.aspx |
Research directions
1. Cancer epigenetics of major tumours in Hong Kong
Epigenetic regulation of transcription through promoter CpG methylation is a fundamental regulatory process of gene expression. CpG methylation strongly represses promoter activity, and normally is a cellular defence mechanism against invasive DNA materials. Methylation is important for embryonic development, tissue-specific gene expression and genetic imprinting. In tumours, aberrant hypermethylation of tumour suppressor gene (TSG) promoters silences their expression, resulting in the loss of TSG functions and contributing to tumorigenesis, similar to genetic mutations.
Hong Kong is a developed and densely-populated city. Cancer has been the leading cause of death in Hong Kong for years, which causes serious social and economic problems. It is well established that at molecular levels, carcinogenesis is a multi-step process involving the disruption of multiple genes by either genetic or epigenetic mechanisms. The presence of epigenetic abnormalities provides us with not only potential epigenetic tumour markers for molecular diagnosis and therapeutics, but also a novel way of identifying candidate TSGs. Theoretically, frequent epigenetic inactivation of a candidate gene specifically in tumours but not in the corresponding normal tissues indicates that it is probably a genuine TSG. For some TSGs, only the epigenetic inactivation can be found in tumours, while their genetic alterations are rare, such as RASSF1A. This type of genes is now called as Class two (new-age) tumour suppressor genes.
Hypermethylation of TSG promoters has been detected not only in primary tumours, but also in serum, sputum, stool, bodily fluids, ductal lavage fluid and saliva of cancer patients. Thus, it can be used as a non-invasive molecular diagnostic marker. Moreover, promoter methylation can be reversed by using DNA methyltransferase (DNMT) inhibitors (5-aza-2′-deoxycytidine – decitabine or 5-aza-cytidine). Clinical trials using these agents have been carried out in several research centres including ours, on myelodysplastic syndrome patients and cancer patients with colon, head, neck, renal, lung tumours and nasopharyngeal carcinoma (NPC). These trials were designed to demethylate and reactivate hypermethylated and silenced genes and thus restore normal cell growth control or induce apoptosis in tumour cells.
My major research interest is the identification of new TSG candidates, which are inactivated by hypermethylation in major tumours in Hong Kong (including NPC, nasal lymphoma and other common carcinomas), by using various subtractive, cancer genomic and epigenomic, and microarray analyses. I further aim to study the regulation and functions of these identified genes, and use them to develop molecular diagnostic and therapeutic strategies towards these tumours (Fig. 1).
G8 can inhibit tumour cell colony formation, same as p53, thus is a functional TSG.
2. Molecular pathogenesis of Epstein-Barr virus (EBV) in NPC and nasal lymphoma
EBV is a ubiquitous herpes virus with worldwide infection. EBV is a transforming virus which can immortalize B-cells and cause lymphomas in animal models. It is strongly associated with a variety of tumours, including Burkitt’s lymphoma, NPC, nasal lymphoma, posttransplant lymphoma, Hodgkin’s disease, and AIDS-lymphoma. Both NPC and nasal lymphoma are prevalent tumours in Hong Kong.
NPC is a major tumour killer for Chinese in a few places in Asia, including Southern China (Hong Kong) and Southeast Asia (Singapore), reaching an incidence of 30-50/100,000/year. It is the fourth most common tumour in Hong Kong. Each year, around 1,100 new cases of NPC were diagnosed in Hong Kong, and about 400 patients died of this disease. Histologically, this tumour usually belongs to the WHO types II and III: non-keratinising and undifferentiated carcinoma. Various studies on its aetiology suggest that both environmental (such as diet, EBV) and genetic/epigenetic factors contribute to its pathogenesis. As for EBV, it is associated with virtually all NPC, regardless of geographic distribution, ethnic origin and local prevalence of the disease. The presence of EBV in NPC provides us with novel diagnostic and therapeutic targets.
Nasal NK/T cell lymphoma (NL) occurs in the nose and midfacial region, and clinically used to be called as “lethal midline granuloma” to describe its necrotic and ulcerative features. In Western countries, nasal lymphoma is uncommon, comprising only 0.44% of all extranodal lymphoma and 0.17% of all malignant lymphoma. However, it is relatively more common in Oriental populations. In Hong Kong, it is the second most frequent group of extranodal lymphoma after gastrointestinal lymphoma, constituting around 7%-10% of all non-Hodgkin’s lymphoma. NL often shows histologic features of polymorphic cellular infiltration, necrosis and some extent of angiocentricity and angioinvasion, so terms “polymorphic reticulosis” and “angiocentric immunoproliferative lesion” have been used to describe this disease. Clinically, NL often has a poor prognosis.
Both NPC and nasal lymphoma are strongly associated with EBV, with almost 100% viral positivity in tumours. Moreover, EBV exists as a clonal population in these tumours. However, the molecular mechanisms of EBV pathogenesis in these tumours are poorly understood. I am interested in the EBV gene expression and regulation in these tumour models, especially the epigenetic regulation of EBV promoters by CpG methylation. Dense CpG methylation silences the transcription of EBV promoters and plays an important role in the regulation of EBV latency. There are four EBV promoters driving the expression of the indispensable viral protein EBNA1. The promoters (Cp and Wp) which drive both EBNA1 and other immunodominant viral proteins are often suppressed by hypermethylation in tumours and meanwhile, EBNA1 expression from the hypomethylated Qp is constitutively maintained. Through this way, EBV lives as latency I and II and escapes from host immune surveillance in tumour patients (Fig. 2).
The potential translational and clinical implications of this line of research are the development of cancer treatment strategies to pharmacologically manipulate the methylation status of viral promoters in tumour patients, thus enhance tumour cell antigenicity and target them for killing by immune system. Our clinical trials in NPC patients have managed to demethylate EBV promoters and reactivate the expression of EBV proteins in NPC tumour cells (Fig. 3).
Representative publications:
| 1. Tao Q, Srivastava G, Loke SL, Liang R, Liu YT, Ho FCS. Epstein-Barr virus (EBV)-related lymphoproliferative disorder with subsequent EBV-negative T-cell lymphoma. Int J Cancer 1994; 58:33-39. |
| 2. Tao Q, Srivastava G, Loke SL, Ho FCS. Lack of correlation between the expression of Epstein-Barr virus (EBV) latent membrane protein and bcl-2 in vivo. J Clin Pathol 1994; 47:589-591. |
| 3. Tao Q, Srivastava G, Chan ACL, Ho FCS. Epstein-Barr virus-infected nasopharyngeal intraepithelial lymphocytes. Lancet 1995; 345:1309-1310. |
| 4. Tao Q, Srivastava G, Chan ACL, Chung LP, Loke SL, Ho FCS. Evidence for lytic infection by Epstein-Barr virus in mucosal lymphocytes instead of nasopharyngeal epithelial cells in normal individuals. J Med Virol 1995; 45:71-77. |
| 5. Tao Q, Ho FCS, Loke SL, Srivastava G. Epstein-Barr virus is localized in the tumor cells of nasal lymphomas of NK, T or B cell type. Int J Cancer 1995; 60:315-320. |
| 6. Tao Q, Srivastava G, Dickens P, Ho FCS. Detection of Epstein-Barr virus-infected mucosal lymphocytes in nasal polyps. Am J Pathol 1996; 149:1111-1118. |
| 7. Chiang AKS*, Tao Q*, Srivastava G, Ho FCS. Nasal NK- and T-cell lymphomas share the same type of Epstein-Barr virus latency as nasopharyngeal carcinoma and Hodgkin’s disease. Int J Cancer 1996; 68:285-290. (*: co-first author) |
| 8. Tao Q, Robertson KD, Manns A, Hildesheim A, Ambinder RF. Epstein-Barr virus (EBV) in endemic Burkitt’s lymphoma: molecular analysis of primary tumor tissue. Blood 1998; 91:1373-1381. |
| 9. Tao Q, Robertson KD, Manns A, Hildesheim A, Ambinder RF. The Epstein-Barr virus major latent promoter Qp is constitutively active, hypomethylated, and methylation-sensitive. J Virol 1998; 72:7075-7083. |
| 10. Tao Q, Swinnen L, Yang J, Srivastava G, Robertson KD, Ambinder RF. Methylation status of the Epstein-Barr Virus major latent promoter C in iatrogenic B-cell lymphoproliferative disease: application of PCR-based analysis. Am J Pathol 1999; 155:619-625. |
| 11. Ambinder RF, Robertson KD, Tao Q. DNA methylation and the Epstein-Barr virus (Review). Semin Cancer Biol 1999; 9:369-375. |
| 12. Srivastava G, Wong KY, Chiang AKS, Lam KY, Tao Q. Coinfection of multiple strains of Epstein-Barr virus in immunocompetent normal individuals: reassessment of the viral carrier state. Blood 2000; 95:2443-2445. |
| 13. Yang J, Tao Q, Flinn IW, Murray PG, Post L, Ma H, Piantadosi S, Caligiuri MA, Ambinder RF. Characterization of EBV-infected B cells in patients with PTLD; disappearance after Rituximab therapy does not predict clinical response. Blood 2000; 96:4055-4063. |
| 14. Tao Q, Yang J, Huang H, Swinnen L, Ambinder RF. Conservation of Epstein-Barr virus cytotoxic T cell epitopes in posttransplant lymphomas: implications for immune therapy. Am J Pathol 2002; 160:1839-1845. |
| 15. Tao Q, Huang H, Geiman TM, Lim CY, Fu L, Qiu GH, Robertson KD. Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells. Human Mol Genetics 2002; 11:2091-2102. |
| 16. Tao Q and Robertson KD. Stealth Technology: How Epstein-Barr virus (EBV) utilizes DNA methylation to cloak itself from immune detection (Review). Clinical Immunol 2003; 109:53-63. |
| 17. Ying J, Srivastava G, Gao Z, Zhang XH, Murray P, Ambinder R, Tao Q. Promoter hypermethylation of the Cyclin-dependent kinase inhibitor (CDKI) gene p21WAF1/CIP1/SDI1 is rare in various lymphomas and carcinomas. Blood 2004; 103:743-746. |
| 18. Murray PG, Qiu GH, Fu L, Waites ER, Srivastava G, Agathanggelou A, Latif F, Grundy RG, Mann JR, Starczynski J, Crocker J, Parkes SE, Ambinder RF, Young LS, Tao Q. Frequent epigenetic inactivation of the RASSF1A tumor suppressor gene in Hodgkin’s lymphoma. Oncogene 2004; 23:1326-1331. |
| 19. Chan AT*, Tao Q*, Robertson KD, Flinn IW, Mann RB, Klencke B, Leung T, Johnson PJ, Ambinder RF (*: Co-first author). Azacitidine Induces Demethylation of the Epstein-Barr Virus Genome in Tumors in Patients. J Clin Oncol 2004; 22:1373-1381. (Editorial by Dowell JE & Minna JD. Cancer Chemotherapy Targeted at Reactivating the Expression of Epigenetically Inactivated Genes. JCO 2004; 22: 1353–1355). |
| 20. Qiu GH, Tan LKS, Loh KS, Lim CY, Srivastava G, Tsai ST, Tsao SW, Tao Q. The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene, and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma. Oncogene 2004; 23:4793-4806. |
| 21. Ying J, Srivastava G, Hsieh WS, Gao Z, Murray P, Liao SK, Ambinder R, Tao Q. The Stress-responsive Gene GADD45G Is a Functional Tumor Suppressor, with Its Response to Environmental Stresses Frequently Disrupted Epigenetically in Multiple Tumors. Clin Cancer Res 2005; 11:6442-6449. (Editorial by Zerbini LF & Libermann TA. GADD45 Deregulation in Cancer. Clin Cancer Res. 2005; 11:6409-13) |
| 22. Zhou L, Jiang W, Ren C, Yin Z, Feng X, Liu W, Tao Q, Yao K. Frequent hypermethylation of RASSF1A and TSLC1 and high viral load of Epstein-Barr virus DNA in nasopharyngeal carcinoma and matched tumor-adjacent tissues. Neoplasia 2005; 7:809-815. |
| 23. Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao SW, Putti T, Murray P, Chan ATC, Tao Q. Functional epigenetics identifies a protocadherin – PCDH10 as a tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene 2006; 25:1070-80. |
| 24. Wong MLY, Tao Q*, Fu L, Wong KY, Qiu GH, FBF Law, Tin PC, Cheung WL, Lee PY, Tang JCO, Tsao GSW, Lam KY, Law S, Wong J, Srivastava G*. (*Corresponding authors). Aberrant promoter hypermethylation and silencing of the critical 3p21 tumor suppressor gene RASSF1A in Chinese esophageal squamous cell carcinoma. Int J Oncol 2006; 28:767-773. |
| 25. Tao Q, Young LS, Woodman CBJ, Murray PG. Epstein-Barr virus (EBV) and its associated human cancers – Genetics, epigenetics, pathobiology and novel therapeutics (Invited review). Front Biosci 2006; 11:2672-2713. |
| 26. Ai L, Tao Q, Zhong S, Fields CR, Kim WJ, Lee MW, Cui Y, Brown KD, Robertson KD. Inactivation of Wnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in breast cancer. Carcinogenesis 2006; 27:1341-1348. |
| 27. Ying J, Li H, Cui Y, Wong AHY, Langford C, Tao Q. Epigenetic disruption of two proapoptotic genes MAPK10/JNK3 and PTPN13/FAP-1 in multiple lymphomas and carcinomas through hypermethylation of a common bidirectional promoter. Leukemia 2006; 20:1173-5. |
| 28. Chen YW, Hu X, Liang ACT, Au WY, Wong MLY, Shen L, Tao Q, Chu KM, Kwong YL, Liang R, Srivastava G. High BCL6 expression predicts better prognosis independent of BCL6 translocation status or presence of Ig/BCL6 or non-Ig/BCL6 translocations or BCL6 deregulating mutations in non-coding exon 1 in gastric lymphoma. Blood 2006; 108:2373-83. |
| 29. Soo RA, Wu J, Aggarwal A, Tao Q, Hsieh W, Putti T, Tan KB, Low JSW, Lai YF, Mow B, Hsu S, Loh KS, Tan L, Tan P, Goh BC. Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression. Ann Oncol 2006; 17:1625-30. |
| 30.Seng TJ, Low JSW, Li H, Cui Y, Goh HK, Wong MLY, Srivastava G, Sydransky D, Califano J, Steenbergen RDM, Rha SY, Tang J, Hsieh WS, Ambinder R, Lin X, Chan ATC, Tao Q. The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation. Oncogene 2007; 26:934-44. |
| 31. Zhang Q, Ying J, Zhang K, Li H, Ng KM, Zhao Y, He Q, Yang X, Xin D, Liao SK, Tao Q*, Jin J*. (*Corresponding authors). Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell carcinoma. Cancer Letter 2007; 249:220-226. |
| 32. Ying J, Gao Z, Li H, Srivastava G, Murray PG, Goh HK, Lim CY, Wang Y, Marafioti T, Mason DY, Ambinder RF, Chan ATC, Tao Q. Frequent epigenetic silencing of protocadherin 10 by methylation in multiple hematologic malignancies. Br J Hematol 2007; 136:829-832.Table S1 Table S2 |
| 33. Sung FL, Hui EP, Tao Q, Li H, Tsui NBY, Lo YMD, Ma BBY, To KF, Harris AL, Chan ATC. Genome-wide expression analysis using microarray identified complex signaling pathways modulated by hypoxia in nasopharyngeal carcinoma. Cancer Letter 2007; 253:74-88. |
| 34. Tao Q, Chan ATC. Nasopharyngeal carcinoma – Molecular pathogenesis and therapeutic developments. (Invited review) Expert Rev Mol Med. 2007; 9:1-24. |
| 35. Chan SL, Cui Y, van Hasselt A, Li H, Srivastava G, Jin H, Ng KM, Wang Y, Lee KY, Tsao GSW, Zhong S, Robertson KD, Rha SY, Chan ATC, Tao Q. The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas. Lab Invest 2007; 87:644-50. |
| 36. Law FBF, Chen YW, Wong KY, Ying J, Tao Q, Langford C, Lee PY, Law S, Cheung RWL, Chui CH, Tsao GSW, Lam KY, Wong J, Srivastava G, Tang JCO. Identification of a novel tumor transforming gene GAEC1 at 7q22 which encodes a nuclear protein and is frequently amplified and overexpressed in esophageal squamous cell carcinoma. Oncogene 2007; 26:5877-88. |
| 37. Ying J, Li H, Murray P, Gao Z, Chen YW, Wang Y, Lee KY, Chan ATC, Ambinder RF, Srivastava G*, Tao Q*. (*Corresponding authors). Tumor-specific methylation of the 8p22 tumor suppressor gene DLC1 is an epigenetic biomarker for Hodgkin, nasal NK/T-cell and other types of lymphomas. Epigenetics 2007; 2:15-21. |
| 38. Shao L, Cui Y, Li H, Liu Y, Zhao H, Wang Y, Zhang Y, Ng KM, Han W, Ma D*, Tao Q* (*Corresponding authors). CMTM5 exhibits tumor suppressor activities and is frequently silenced by methylation in carcinoma cell lines. Clin Cancer Res 2007; 13:5756-62. |
| 39. Cheng YY, Yu J, Wong YP, Man EPS, To KF, Jin VX, Li J, Tao Q, Sung JJY, Chan FKL, Leung WK. Frequent epigenetic inactivation of secreted frizzled-related protein 2 (SFRP2) by promoter methylation in human gastric cancer. Br J Cancer 2007; 97:895-901. |
| 40. Bose S, Starczynski J, Chukwuma M, Baumforth K, Wei W, Morgan S, Byrd P, Ying J, Grundy R, Mann JR, Tao Q, Taylor AMR, Murray PG, Stankovic T. Down-regulation of ATM protein in HRS cells of nodular sclerosis Hodgkin’s lymphoma in children occurs in the absence of ATM gene inactivation. J Pathol 2007; 213:329-36. |
| 41. Tedoldi S, Mottok A, Ying J, Paterson, J, Cui Y, Facchetti F, van Krieken JH, Ponzoni M, Ozkal S, Masir N, Natkunam Y, Pileri SA, Hansmann ML, Mason DY*, Tao Q*, Marafioti T* (*equal contribution). Selective loss of B-cell phenotype in lymphocyte predominant Hodgkin lymphoma. J Pathol 2007; 213:429-40. |
| 42. Jin H, Wang X, Ying J, Wong AHY, Li H, Lee KY, Srivastava G, Chan ATC, Yeo W, Ma BBY, Putti TC, Lung ML, Shen ZY, Xu LY, Langford C, Tao Q. Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas. Oncogene 2007; 26:7490-8. Epub 2007 Jun 4. |
| 43. Zhang Q, Jin J, Tao Q. Aberrant methylation of tumor suppressor genes in renal cell carcinoma (review). Ai Zheng (Chinese J Cancer). 2007; 26:1276-80. |
| 44. Ying J, Li H, Chen YW, Srivastava G, Gao Z, Tao Q. WNT5A is epigenetically silenced in hematologic malignancies and inhibits leukemia cell growth as a tumor suppressor. Blood 2007; 110:4130-1. |
| 45. Jin H, Wang X, Ying J, Wong AHY, Cui Y, Srivastava G, Shen ZY, Li EM, Zhang Q, Jin J, Kupzig S, Chan ATC, Cullen PJ, Tao Q. Epigenetic silencing of a Ca(2+)-regulated Ras GTPase-activating protein RASAL defines a new mechanism of Ras activation in human cancers. Proc Natl Acad Sci USA 2007; 104:12353-8. |
| 46. Ying J, Li H, Yu J, Ng KM, Poon FF, Wong SCC, Chan ATC, Sung JJY, Tao Q. WNT5A exhibits tumor-suppressive activity through antagonizing the Wnt/β-catenin signaling, and is frequently methylated in colorectal cancer. Clin Cancer Res 2008; 14:55-61. |
| 47. Jin B, Tao Q, Peng J, Soo HM, Wu W, Ying J, Fields CR, Delmas AL, Liu X, Qiu J, Robertson KD. DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis, and immune function. Human Mol Genet 2008; 17:690-709. Epub 2007 Nov 20. |
| 48. Qiu GH, Salto-Tellez M, Ross JA, Yeo W, Cui Y, Wheelhouse N, Chen GG, Harrison D, Lai P, Tao Q*, Hooi SC*. (*Corresponding authors). The tumor suppressor gene DLEC1 is frequently silenced by DNA methylation in hepatocellular carcinoma and induces G1 arrest in cell cycle. J Hepatol 2008; 48:433-41. Epub 2007 Dec 31. |
| 49. Chan SYY, Choy KW, Tsao SW, Tao Q, Tang T, Chung GTY, Lo KW. Authentication of Nasopharyngeal Carcinoma Tumor Lines. Int J Cancer 2008; 122:2169-71. Jan 14, online. |
| 50. Yu J, Tao Q*, Cheung KF, Jin H, Poon FF, Wang X, Li H, Cheng YY, Ebert MPA, Rocken C, Chan ATC, Sung JJY*. (*Corresponding authors). Epigenetic identification of UCHL1 as a functional tumor suppressor and biomarker for hepatocellular carcinoma and other digestive tumors. Hepatol 2008; 48(2):508-18. |
| 51. Lee KY*, Geng H*, Ng KM, Yu J, van Hasselt A, Cao Y, YX Zeng, Wong AHY, Wang X, Ying J, Srivastava G, Lung ML, Wang LD, Levi BZ, Kwok TT, Chan ATC, Sung JJY, Tao Q. Epigenetic disruption of interferon-gamma response through silencing the tumor suppressor Interferon Regulatory Factor 8 (IRF8) in nasopharyngeal, esophageal and multiple other carcinomas. Oncogene 2008; May 12, online. |
| 52. Cui Y*, Ying Y*, van Hasselt A, Ng KM, Yu J, Zhang Q, Jin J, Liu D, Rhim JS, Rha SY, Loyo M, Chan ATC, Srivastava G, Sellar GC, Sidransky D, Tao Q. OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. PLoS One 2008; 3:e2990. |
| 53. Cui L, Xu LY, Shen ZY, Tao Q, Gao SY, Lv Z, Du ZP, Fang WK, Li EM. NGALR is overexpressed and regulated by hypomethylation in esophageal squamous cell carcinoma. Clin Cancer Res 2008; 14:7674-7681. |
| 54. Fu L, Gao Z, Zhang X, Tsang YH, Goh HK, Geng H, Shimizu N, Tsuchiyama J, Srivastava G, Tao Q. Frequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1 and its interacting partner DAL-1 in nasal NK/T-cell lymphoma. Int J Cancer 2009; 124:1572-8. |
| 55. Yu J, Tao Q, Cheng YY, Wong AHY, Cheung KF, Tian L, Ebert MPA, Rocken C, Chan FKL, Leung WK, Sung JJY. Promoter methylation of the WNT/b-catenin signaling antagonist DKK3 gene is associated poor survival of gastric cancer. Cancer 2009; 115:49-60. lymphoma. Int J Cancer 2008; in press. |
| 56. Ying J, Poon FF, Yu J, Geng H, Wong AHY, Qiu GH, Goh HK, Rha SY, Tian L, Chan ATC, Sung JJY, Tao Q. DLEC1 is a functional 3p22.3 tumor suppressor silenced by promoter CpG methylation in colon and gastric cancers. Br J Cancer 2009; 100:663-9. |
| 57. Ma BBY, Sung F, Tao Q, Poon FF, Lui V, Yeo W, Chan SL, Lin XR, Chan ATC. The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat) in hepatocellular carcinoma cell lines. Invest New Drugs 2009 Jan 27. online. |
| 58. Yu J, Cheng YY, Tao Q, Cheung KF, Lam CNY, Geng H, Tian LW, Wong YP, Tong JHM, Ying J, Jin H, To KF, Chan FKL, Sung JJY. Methylation of protocadherin 10, a novel tumor-suppressor, is associated with poor prognosis in patients with gastric cancer. Gastroenterol 2009; 136:640-51.e1. |
| 59. Hu XT, Zhang FB, Fan YC, Shu XS, Wong AHY, Zhou W, Shi QL, Tang HM, Fu L, Guan XY, Rha SY, Tao Q*, He C* (*Corresp authors). Phospholipase C delta 1 is a 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high stage gastric cancer. Oncogene 2009; in press. |
| 60. Wang Y, Li J, Cui Y, Li T, Ng KM, Geng H, Li H, Shu XS, Li H, Liu W, Luo B, Zhang Q, Mok TSK, Zheng W, Qiu X, Srivastava G, Yu J, Sung JJY, Chan ATC, Ma D, Tao Q*, Han W* (*Corresp authors). CMTM3, located at the tumor suppressor locus 16q22.1, is silenced by CpG methylation in carcinomas and inhibits tumor cell growth through inducing apoptosis. Cancer Res 2009; in press. |
| 61. Hu XT, Zhang FB, Fan YC, Shu XS, Wong AH, Zhou W, Shi QL, Tang HM, Fu L, Guan XY, Rha SY, Tao Q*, He C* (*Corresp authors). Phospholipase C delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer. Oncogene 2009; 28:2466-75. |
| 62. Wang Y, Li J, Cui Y, Li T, Ng KM, Geng H, Li H, Shu XS, Li H, Liu W, Luo B, Zhang Q, Mok TSK, Zheng W, Qiu X, Srivastava G, Yu J, Sung JJY, Chan ATC, Ma D, Tao Q*, Han W* (*Corresp authors). CMTM3, located at the critical tumor suppressor locus 16q22.1, is silenced by CpG methylation in carcinomas and inhibits tumor cell growth through inducing apoptosis. Cancer Res 2009; 69:5194-5201. |
| 63. Ying Y, Tao Q. Epigenetic disruption of the WNT/s-catenin signaling pathway in human cancers (review). Epigenetics 2009; 4:307-12. |
| 64. Narayan G, Scotto L, Neelakantan V, Kottoor SH, Wong AHY, Loke SL, Mansukhani M, Pothuri B, Wright JD, Kaufmann AM, Schneider A, Arias-Pulido A, Tao Q, Murty VV. Protocadherin PCDH10, Involved in tumor Progression, is a Frequent and early Target of Promoter Hypermethylation in Cervical Cancer. Genes, Chr Cancer 2009; 48:983-992. |
| 65. Ma BB, Lui VW, Poon FF, Wong SC, To KF, Wong E, Chen H, Lo KW, Tao Q, Ng MH, Cheng SH, Chan AT. Preclinical activity of gefitinib in non-keratinizing nasopharyngeal carcinoma cell lines and biomarkers of response. Invest New Drugs 2010; 28:326-33. |
| 66. Zhang Q, Ying J, Li J, Fan Y, Poon FF, Ng KM, Tao Q*, Jin J* (*Corresp authors). Aberrant promoter methylation of DLEC1, a critical 3p22 tumor suppressor for renal cell carcinoma, is associated with more advanced tumor stage. J Urol 2010; 184:731-7. |
| 67. Ma BB, Sung F, Tao Q, Poon FF, Lui V, Yeo W, Chan SL, Chan AT. The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat) in hepatocellular carcinoma cell lines. Invest New Drugs 2010; 28:107-1 |
| 68. Fu L, Dong SS, Xie YW, Tai LS, Chen L, Kong KL, Man K, Xie D, Li Y, Cheng Y, Tao Q, Guan XY. Down-regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma. Hepatol 2010; 51:1624-34. |
| 69. Hu XT, Chen YW, Liang AC, Au WY, Wong KY, Wan TS, Wong ML, Shen L, Chan KK, Guo T, Chu KM, Tao Q, Chim CS, Loong F, Choi WW, Lu L, So CC, Chan LC, Kwong YL, Liang R, Srivastava G. CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation. Blood 2010; 115:2458-61. |
| 70. Li J, Ying J, Fan Y, Wu L, Ying Y, Chan AT, Srivastava G, Tao Q. WNT5A antagonizes WNT/β-catenin signaling and is frequently silenced by promoter CpG methylation in esophageal squamous cell carcinoma. Cancer Biol Ther 2010; 10:617-24. |
| 71. Li L, Tao Q*, Jin H, van Hasselt A, Poon FF, Wang X, Zeng MS, Jia WH, Zeng YX, Chan AT*, Cao Y* (*Corresp authors). The tumor suppressor UCHL1 forms a complex with p53/MDM2/ARF to promote p53 signaling and is frequently silenced in nasopharyngeal carcinoma. Clin Cancer Res 2010; 16:2949-58. |
| 72. Murray PG, Fan Y, Davies G, Ying J, Geng H, Ng KM, Li H, Gao Z, Wei W, Bose S, Anderton J, Kapatai G, Reynolds G, Ito A, Marafioti T, Woodman CB, Ambinder R, Tao Q. Epigenetic Silencing of a Proapoptotic Cell Adhesion Molecule, the Immunoglobulin Superfamily Member IGSF4, by Promoter CpG Methylation Protects Hodgkin Lymphoma Cells from Apoptosis. Am J Pathol 2010; 177:1480-1490. |
| 73. Xiang T, Li L, Fan Y, Jiang Y, Ying Y, Putti TC, Tao Q*, Ren G* (*Corresp authors). PLCD1 is a functional tumor suppressor inducing G(2)/M arrest and frequently methylated in breast cancer. Cancer Biol Ther 2010; 10:520-7. |
| 74. Chan SH, Ko JM, Chan KW, Chan YP, Tao Q, Hyytiainen M, Keski-Oja J, Law S, Srivastava G, Tang J, Tsao SW, Chen H, Stanbridge EJ, Lung ML. The ECM protein LTBP-2 is a suppressor of esophageal squamous cell carcinoma tumor formation but higher tumor expression associates with poor patient outcome. Int J Cancer 2010; 129:565-73. |
| 75. Cheng Y, Geng H, Cheng SH, Liang P, Bai Y, Li J, Srivastava G, Ng MH, Fukagawa T, Wu X, Chan AT, Tao Q. KRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas. Cancer Res 2010; 70:6516-26. |
| 76. Loyo M, Brait M, Kim MS, Ostrow KL, Chie CJ, Chuang AY, Califano JA, Liegeois NJ, Begum S, Westra WH, Hoque MO, Tao Q, Sidransky D. A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma. Int J Cancer 2011; 128:1393-403. |
| 77. Liu W, Li X, Chu ES, Go MY, Xu L, Zhao G, Li L, Dai N, Si J, Tao Q, Sung JJ, Yu J. Paired box gene 5 is a novel tumor suppressor in hepatocellular carcinoma through interaction with p53 signaling pathway. Hepatology 2011; 53:843-53. |
| 78. Zhou JW, Tsui SK, Ng MC, Geng H, Li SK, So WY, Ma RC, Wang Y, Tao Q, Chen ZY, Chan JC, Ho YY. Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes. PLoS One 2011; 6:e17324. |
| 79. Li L, Shu XS, Wang ZH, Cao Y, Tao Q. Epigenetic disruption of cell signaling in nasopharyngeal carcinoma. Chinese J Cancer 2011; 30:231-9. |
| 80. Low JS, Tao Q*, Ng KM, Goh HK, Shu XS, Woo WL, Ambinder RF, Srivastava G, Shamay M, Chan AT, Popescu NC, Hsieh WS* (*Corresp authors). A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors. Oncogene 2011; 30:1923-35. |
| 81. Li JS, Ying J, Wang WX, Wang ZH, Tao Q, Li L. Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma. Chinese J Cancer 2012 May 8. doi: 10.5732/cjc.011.10381. |
| 82. Shu XS*, Geng H*, Li L, Ying J, Ma C, Wang Y, Poon FF, Wang X, Ying Y, Yeo W, Srivastava G, Tsao SW, Yu J, Sung JJ, Huang S, Chan AT, Tao Q. The Epigenetic Modifier PRDM5 Functions as a Tumor Suppressor through Modulating WNT/β-Catenin Signaling and Is Frequently Silenced in Multiple Tumors. PLoS One 2011; 6:e27346. |
| 83. Zhu Z, Huang YJ, Tao Q, Li Q. Cellular uptake, evolution, and excretion of silica nanoparticles in human cells. Nanoscale 2011; 3:3291-9. |
| 84. Xiang TX, Yuan Y, Li LL, Wang ZH, Dan LY, Chen Y, Ren GS, Tao Q. Aberrant promoter CpG methylation and its translational applications in breast cancer. Chin J Cancer 2011 Nov 4. doi: 10.5732/cjc.011.10344. |
| 85. Li L, Ying J, Li H, Zhang Y, Shu XS, Fan Y, Tan J, Cao Y, Tsao SW, Srivastava G, Chan AT, Tao Q. The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through WNT/β-catenin signaling and silenced in common carcinomas. Oncogene 2012; 31:3901-12. |
| 86. Xu L, Li X, Chu ES, Zhao G, Go MY, Tao Q, Jin H, Zeng Z, Sung JJ, Yu J. Epigenetic inactivation of BCL6B, a novel functional tumor suppressor for gastric cancer, is associated with poor survival of gastric cancer. Gut 2012; 61:977-85. |
| 87. Li X, Cheung KF, Ma X, Tian L, Zhao J, Go MY, Shen B, Cheng AS, Ying J, Tao Q, Sung JJ, Kung HF, Yu J. Epigenetic inactivation of paired box gene 5, a novel tumor suppressor gene, through direct upregulation of p53 is associated with prognosis in gastric cancer patients. Oncogene 2012; 31(29):3419-30. |
| 88. Xiang T, Li L, Yin X, Yuan C, Tan C, Su X, Xiong L, Putti TC, Oberst M, Kelly K, Ren G, Tao Q. The ubiquitin peptidase UCHL1 induces G0/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancer. PLoS One 2012; 7:e29783. |
| 89. Yu J, Liang Q, Wang J, Cheng Y, Wang S, Poon TC, Go MY, Tao Q, Chang Z, Sung JJ. Zinc Finger Protein 331, a novel putative tumor suppressor, suppresses growth and invasiveness of gastric cancer. Oncogene 2012; Feb 27. doi: 10.1038/onc.2012.54. |
| 90. Yeo W, Chung HC, Chan SL, Wang LZ, Lim R, Picus J, Boyer M, Mo FK, Koh J, Rha SY, Hui EP, Jeung HC, Roh JK, Yu SC, To KF, Tao Q, Ma BB, Chan AW, Tong JH, Erlichman C, Chan AT, Goh BC. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: A multicenter phase I/II study with biomarker and pharmacokinetic analysis of the Mayo Phase 2 Consortium (P2C) and the Cancer Therapeutics Research Group (CTRG). J Clin Oncol 2012; 30:3361-7. |
| 91. Li L, Li W, Xiao L, Xu J, Chen X, Tang M, Dong Z, Tao Q, Cao Y. Viral oncoprotein LMP1 disrupts p53-induced cell cycle arrest and apoptosis through modulating K63-linked ubiquitination of p53. Cell Cycle 2012; 11:2327-36. |
| 92. Wang S, Cheng Y, Du W, Lu L, Zhou L, Wang H, Kang W, Li X, Tao Q*, Sung JJ, Yu J*. Zinc-finger protein 545 is a novel tumor suppressor that acts by inhibiting ribosomal RNA transcription in gastric cancer. Gut 2012 May 12. [Epub ahead of print] |
| 93. Li L, Su X, Choi GC, Cao Y, Ambinder RF, Tao Q. Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1 and BRLF1 in tumors of epithelial, NK- and B-cell origins. BMC Cancer 2012; 12:125. |
| 94. Ying J, Shan L, Li J, Zhong L, Xue L, Zhao H, Li L, Langford C, Guo L, Qiu T, Lu N, Tao Q. Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis. PLoS One 2012; 7:e39797. |
| 95. Cheng Y, Liang P, Geng H, Wang Z, Li L, Cheng SH, Ying J, Su X, Ng KM, Ng MH, Mok TS, Chan AT, Tao Q. A Novel 19q13 Nucleolar Zinc Finger Protein Suppresses Tumor Cell Growth through Inhibiting Ribosome Biogenesis and Inducing Apoptosis but Is Frequently Silenced in Multiple Carcinomas. Mol Cancer Res 2012; 10:925-36. |
| 96. Chen H, Ko JM, Wong VC, Hyytiainen M, Keski-Oja J, Chua D, Nicholls JM, Cheung FM, Lee AW, Kwong DL, Chiu PM, Zabarovsky ER, Tsao SW, Tao Q, Kan R, Chan SH, Stanbridge EJ, Lung ML. LTBP-2 confers pleiotropic suppression and promotes dormancy in a growth factor permissive microenvironment in nasopharyngeal carcinoma. Cancer Lett 2012; 325:89-98. |
| 97. Chu Z, Huang Y, Li L, Tao Q, Li Q. Physiological pathway of human cell damage induced by genotoxic crystalline silica nanoparticles. Biomaterials 2012; 33:7540-6. |
| 98. Du W, Wang S, Zhou Q, Li X, Chu J, Tao Q, Fang J, Sung JJ, Yu J. ADAMTS9 is a functional tumor suppressor through inhibiting AKT/mTOR pathway and associated with poor survival in gastric cancer. Oncogene 2012 Aug 20. doi: 10.1038/onc.2012.359. |
| 99. Fok KL, Chung CM, Yi SQ, Jiang XH, Sun X, Chen H, Chen YC, Kung HF, Tao Q, Diao R, Chan H, Zhang XH, Chung YW, Cai Z, Chan HC. STK31 maintains the undifferentiated state of colon cancer cells. Carcinogenesis 2012 Aug 28. [Epub ahead of print] |
| 100. Hu X, Sui X, Li L, Huang X, Rong R, Su X, Shi Q, Mo L, Shu X, Kuang Y, Tao Q*, He C* (*Corresp authors). Protocadherin 17 acts as a tumor suppressor inducing tumor cell apoptosis and autophagy, and is frequently methylated in gastric and colorectal cancers. J Pathol 2012 Aug 27. doi: 10.1002/path.4093. |
| 101. Wang Z, Li Li, Su X, Gao Z, Srivastava G, Murray PG, Ambinder R, Tao Q. Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-Hodgkin and Hodgkin lymphomas. J Transl Med 2012; 10:209. |
| 102. Liu X, Wang Y, Wang X, Sun Z, Li L, Tao Q, Luo B. Epigenetic silencing of WNT5A permits Wnt/β-catenin signaling activation in Epstein-Barr virus-associated gastric carcinoma. Arch Virol 2012 Sep 23. [Epub ahead of print] |
| 103. Vrzalikova K, Leonard S, Fan Y, Bell A, Vockerodt M, Flodr P, Wright K, Rowe M, Tao Q, Murray P. Hypomethylation and over-expression of the beta isoform of BLIMP1 is induced by Epstein-Barr virus infection of B cells: potential implications for the pathogenesis of EBV-associated lymphomas. Pathogens 2012; 1(2):83-101. |
| 104. Wang S, Go MY, Kang W, Chu ES, Cheung KF, Tong JH, Li L, Tao Q, Li X, To KF, Sung JJ, Yu J. Dapper homolog 1 is a novel tumor suppressor in gastric cancer through inhibiting nuclear factor-kappa B and planar cell polarity pathways. Mol Med 2012; in press |
| 105. Shu XS, Li L, Tao Q. Chromatin regulators with tumor suppressor properties and their alternations in human cancers. Epigenomics 2012; in press. |
| 106. Hu X, Sui X, Li L, Huang X, Rong R, Su X, Shi Q, Mo L, Shu X, Kuang Y, Tao Q*, He C* (*corresponding authors). Protocadherin 17 acts as a tumor suppressor inducing tumor cell apoptosis and autophagy, and is frequently methylated in gastric and colorectal cancers. J Pathol 2013; 229:62-73. |
| 107. 2. Wang J, Xia Y, Li L, Gong D, Yao Y, Luo H, Lu H, Yi N, Wu H, Zhang X, Tao Q*, Gao F* (*Corresp authors). Double restriction-enzyme digestion improves the coverage and accuracy of genome-wide CpG methylation profiling by reduced representation bisulfite sequencing. BMC Genomics 2013; 14:11. |
| 108. Tao Q. Cancer research in an era when epigeneticcs is no longer “epi” – challenges and opportunities. Chin J Cancer 2013; 32:1-2. |
| 109. 4. Ying X, Xiang T, Li L, Su X, Shu X, Luo X, Huang J, Yuan Y, Peng W, Oberst M, Kelly K, Ren G, Tao Q. DACT1, an antagonist to Wnt/beta-catenin signaling, suppresses tumor cell growth and is frequently silenced in breast cancer. Breast Cancer Res 2013; 15:R23. |
| 110. Su X, Wang Z, Li L, Zheng M, Zheng C, Gong P, Zhao P, Ma Y, Tao Q*, Cai L* (*corresp authors). Lipid-polymer nanoparticles encapsulating doxorubicin and 2′-deoxy-5-azacytidine enhance the sensitivity of cancer cell to chemical therapeutics. Mol Pharm. 2013; 10:1901-9. |
| 111. Li H, Li J, Su Y, Fan Y, Guo X, Li L, Su XW, Rong R, Ying J, Mo X, Liu K, Zhang Z, Yang F, Jiang G, Wang J, Zhang Y, Ma D, Tao Q*, Han W*. A novel 3p22.3 gene CMTM7 represses oncogenic EGFR signaling and inhibits cancer cell growth. Oncogene 2014; 33:3109-18. |
| 112. Shu X, Li L, Ji M, Cheng Y, Ying J, Fan Y, Zhong L, Liu X, Tsao SW, Chan A, Tao Q. FEZF2, a novel 3p14 tumor suppressor gene, represses oncogene EZH2 and MDM2 expression and is frequently methylated in nasopharyngeal carcinoma. Carcinogenesis 2013; 34:1984-93. |
| 113. Xiang T, Li L, Yin X, Zhong L, Peng W, Qiu Z, Ren G*, Tao Q* (*Corresp authors). Epigenetic silencing of the WNT antagonist Dickkopf 3 disrupts normal Wnt/β-catenin signaling and apoptosis regulation in breast cancer cells. J Cell Mol Med 2013; 17:1236-46. |
| 114. Li L, Ying J, Tong X, Su X, Shu X, Rong R, Li H, Chan ATC, Ambinder RF, Guo Y*, Tao Q* (*Corresp authors). Receptor tyrosine kinase-like orphan receptor 2 suppresses β-catenin, AKT signaling and epithelial-mesenchymal transition as a tumor suppressor independent of WNT5A. Cell Mol Life Sci 2013 Oct 25. [Epub ahead of print] |
| 115. Tan Q, Wang G, Huang J, Ding Z, Luo Q, Tony Mok, Tao Q*, Lu S* (*Corresp authors). Epigenomic analysis of lung cancer reveals novel DNA methylation patterns associated with smoking. Onco Targets Ther 2013; 6:1471-9. |
| 116. Zhang Q#, Zhang L#, Li L, Wang L, Ying J, Fan Y, Xu B, Wang L, Liu Q, Chen G*, Tao Q*, Jin J*. Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis. Cancer Lett 2014; in press. |
| 117. Choi GC, Li J, Wang Y, Li L, Zhong L, Ma B, Su X, Ying J, Xiang T, Rha SY, Yu J, Sung JJ, Tsao SW, Chan AT, Tao Q. The Metalloprotease ADAMTS8 Displays Antitumor Properties through Antagonizing EGFR-MEK-ERK Signaling and Is Silenced in Carcinomas by CpG Methylation. Mol Cancer Res 2014; 12:228-38. |
| 118. Wang Y, Lei R, Zhuang X, Zhang N, Pan H, Li G, Hu J, Pan X, Tao Q, Fu D, Xiao J, Chin YE, Kang Y, Yang Q, Hu G. DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis. J Clin Invest. 2014; 124:1646-59. |
| 119. Xiao Y, Xiang T, Luo X, Li C, Li Q, Peng W, Li L, Ren G*, Tao Q* (*Corresp authors). Zinc-finger protein 545 inhibits cell proliferation as a tumor suppressor through inducing apoptosis and is disrupted by promoter methylation in breast cancer PLoS One 2014; in press. |
| 120. L Li, Y Zhang, BB Guo, FKL Chan, Q Tao. Oncogenic induction of cellular high CpG methylation by Epstein-Barr virus in malignant epithelial cells. Chin J Cancer 2014; in press. |
| 121. Tong X, Li L, Li X, Heng L, Zhong L, Hu S, Su X, Liu W, Jia B, Liu X, Kou G, Han J, Guo S, Hu Y, Li C, Tao Q*, Guo Y*. SOX10, a novel HMG-box-containing tumor suppressor, inhibits growth and metastasis of digestive cancers by suppressing the Wnt/β-catenin pathway. Oncotarget 2014; in press. |