A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors

Oncogene

Volumn 30, Issue 16, 2011, Pages 1923-1935

  Low, J S W ^a,b   Tao, Q ^a,c,d   Ng, K M ^d   Goh, H K ^a,b   Shu, X S ^d   Woo, W L ^a   Ambinder, R F ^a,b,c   Srivastava, G ^e   Shamay, M ^a,c   Chan, A T C ^d   Popescu, N C ^f   Hsieh, W S ^a,b,c  

^a Johns Hopkins Singapore   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^c JOHNS HOPKINS UNIVERSITY   (United States)

^d CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^e UNIVERSITY OF HONG KONG   (Hong Kong)

^f NATIONAL CANCER INSTITUTE   (United States)

Author keywords

carcinoma; DLC1; methylation; p53; RhoGAP; tumor suppressor gene

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; DELETED IN LIVER CANCER 1 PROTEIN; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3B; PROTEIN P53; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BREAST CANCER; CANCER GROWTH; CANCER INHIBITION; CARCINOGENESIS; CARCINOMA CELL; COLONY FORMATION; COLORECTAL CANCER; CPG ISLAND; DEMETHYLATION; EPIGENETICS; EPITHELIUM CELL; ESOPHAGUS CANCER; FETUS; GENE SILENCING; HUMAN; HUMAN CELL; HUMAN TISSUE; LIVER CANCER; LUNG CARCINOMA; NASOPHARYNX CANCER; NUCLEOTIDE SEQUENCE; PRIMARY TUMOR; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN METHYLATION; RECEPTOR DOWN REGULATION; SILENCER GENE; STOMACH CANCER; TUMOR CELL LINE; TUMOR SUPPRESSOR GENE; UTERINE CERVIX CANCER;

BASE SEQUENCE; CHROMOSOMES, HUMAN, PAIR 8; DNA METHYLATION; DNA PRIMERS; GENE SILENCING; GENES, TUMOR SUPPRESSOR; GTPASE-ACTIVATING PROTEINS; HUMANS; MOLECULAR SEQUENCE DATA; NEOPLASMS; TUMOR SUPPRESSOR PROTEINS;

EID: 79955466717     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2010.576     Document Type: Article

References (65)

1. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. (1990). Basic local alignment search tool. J Mol Biol 215: 403-410.
2. Bannai H, Tamada Y, Maruyama O, Nakai K, Miyano S. (2002). Extensive feature detection of N-terminal protein sorting signals. Bioinformatics 18: 298-305. (Pubitemid 34183107)
3. Bernards A. (2003). GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila. Biochim Biophys Acta 1603: 47-82. (Pubitemid 36262941)
4. Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP et al. (2005). p53 isoforms can regulate p53 transcriptional activity. Genes Dev 19: 2122-2137. (Pubitemid 41330315)
5. Bullock AN, Fersht AR. (2001). Rescuing the function of mutant p53. Nat Rev Cancer 1: 68-76. (Pubitemid 33741882)
6. Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, Klingenhoff A et al. (2005). MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 21: 2933-2942. (Pubitemid 40916416)
7. Cheung WY, Chan AC, Loke SL, Srivastava G, Pittaluga S, Lim LY et al. (1993). Latent sites of Epstein-Barr virus infection. Am J Clin Pathol 100: 502-506. (Pubitemid 23346197)
8. Ching YP, Wong CM, Chan SF, Leung TH, Ng DC, Jin DY et al. (2003). Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepato-cellular carcinoma. J Biol Chem 278: 10824-10830. (Pubitemid 36800356)
9. Claros MG, Vincens P. (1996). Computational method to predict mitochondrially imported proteins and their targeting sequences. European Journal of Biochemistry 241: 779-786. (Pubitemid 26379380)
10. Cui Y, Ying Y, van Hasselt A, Ng KM, Yu J, Zhang Q et al. (2008). OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. PLoS ONE 3: e2990.
11. Durkin ME, Ullmannova V, Guan M, Popescu NC. (2007a). Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth. Oncogene 26: 4580-4589. (Pubitemid 47037045)
12. Durkin ME, Yuan BZ, Zhou X, Drazen BZ, Douglas RL, Thorgeirsson SS et al. (2007b). DLC-1:a Rho GTPase-activating protein and tumour suppressor. Journal of Cellular and Molecular Medicine 11: 1185-1207. (Pubitemid 350037059)
13. Efeyan A, Serrano M. (2007). p53: guardian of the genome and policeman of the oncogenes. Cell Cycle 6: 1006-1010. (Pubitemid 46708570)
14. Emanuelsson O, Brunak S, von Heijne G, Nielsen H. (2007). Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protocols 2: 953-971. (Pubitemid 46745592)
15. Fearon ER, Vogelstein B. (1990). A genetic model for colorectal tumorigenesis. Cell 61: 759-767.
16. Flicek P, Aken BL, Ballester B, Beal K, Bragin E, Brent S et al. (2010). Ensembl's 10th year. Nucl Acids Res 38: D557-D562.
17. Goodison S, Yuan J, Sloan D, Kim R, Li C, Popescu NC et al. (2005). The RhoGAP protein DLC-1 functions as a metastasis suppressor in breast cancer cells. Cancer Res 65: 6042-6053. (Pubitemid 40994388)
18. Guda C, Fahy E, Subramaniam S. (2004a). MITOPRED: a genome-scale method for prediction of nucleus-encoded mitochondrial proteins. Bioinformatics 20: 1785-1794. (Pubitemid 39162055)
19. Guda C, Guda P, Fahy E, Subramaniam S. (2004b). MITOPRED: a web server for the prediction of mitochondrial proteins. Nucl Acids Res 32: W372-W374. (Pubitemid 38997361)
20. Hall TA. (1999). Bioedit: A user friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 41: 95-98.
21. Heinemeyer T, Chen X, Karas H, Kel AE, Kel OV, Liebich I et al. (1999). Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms. Nucleic Acids Res 27: 318-322. (Pubitemid 29209473)
22. Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel AE, Kel OV et al. (1998). Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Res 26: 362-367. (Pubitemid 28295292)
23. Herman JG, Baylin SB. (2003). Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349: 2042-2054. (Pubitemid 37448928)
24. Homma Y, Emori Y. (1995). A dual functional signal mediator showing RhoGAP and phospholipase C-delta stimulating activities. EMBO J 14: 286-291.
25. Horii A, Nakatsuru S, Ichii S, Nagase H, Nakamura Y. (1993). Multiple forms of the APC gene transcripts and their tissue-specific expression. Hum Mol Genet 2: 283-287. (Pubitemid 23129089)
26. Jones PA, Baylin SB. (2007). The epigenomics of cancer. Cell 128: 683-692. (Pubitemid 46273572)
27. Jones PA, Laird PW. (1999). Cancer epigenetics comes of age. Nat Genet 21: 163-167. (Pubitemid 29070360)
28. Kim TY, Jong HS, Song SH, Dimtchev A, Jeong SJ, Lee JW et al. (2003). Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells. Oncogene 22: 3943-3951. (Pubitemid 36819668)
29. Knudson AG. (2001). Two genetic hits (more or less) to cancer. Nat Rev Cancer 1: 157-162. (Pubitemid 33741891)
30. Ko FC, Yeung YS, Wong CM, Chan LK, Poon RT, Ng IO et al. (2010). Deleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinoma. Liver International 30: 139-148.
31. Kozak M. (1986). Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44: 283-292. (Pubitemid 16048214)
32. Kozak M. (1987). An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res 15: 8125-8148.
33. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H et al. (2007). Clustal W and Clustal x version 2.0. Bioinformatics 23: 2947-2948. (Pubitemid 350162903)
34. Leung TH, Ching YP, Yam JW, Wong CM, Yau TO, Jin DY et al. (2005). Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity. Proc Natl Acad Sci USA 102: 15207-15212. (Pubitemid 41513360)
35. Lo AK, Lo KW, Tsao SW, Wong HL, Hui JW, To KF et al. (2006). Epstein-Barr virus infection alters cellular signal cascades in human nasopharyngeal epithelial cells. Neoplasia 8: 173-180. (Pubitemid 43671232)
36. Maglott D, Ostell J, Pruitt KD, Tatusova T. (2007). Entrez gene: gene-centered information at NCBI. Nucleic Acids Res 35: D26-D31. (Pubitemid 46056164)
37. Martin GS. (2003). Cell signaling and cancer. Cancer Cell 4: 167-174. (Pubitemid 37163830)
38. Moon SY, Zheng Y. (2003). Rho GTPase-activating proteins in cell regulation. Trends Cell Biol 13: 13-22. (Pubitemid 35453891)
39. Ng IO, Liang ZD, Cao L, Lee TK. (2000). DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1. Cancer Res 60: 6581-6584.
40. Pang JC, Chang Q, Chung YF, Teo JG, Poon WS, Zhou LF et al. (2005). Epigenetic inactivation of DLC-1 in supratentorial primitive neuroectodermal tumor. Hum Pathol 36: 36-43. (Pubitemid 40215632)
41. Ponting CP, Aravind L. (1999). START: a lipid-binding domain in StAR, HD-ZIP and signalling proteins. Trends Biochem Sci 24: 130-132. (Pubitemid 29222709)
42. Qiu GH, Tan LK, Loh KS, Lim CY, Srivastava G, Tsai ST et al. (2004). 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 23: 4793-4806. (Pubitemid 38859468)
43. Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE et al. (2002). DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 416: 552-556. (Pubitemid 34288859)
44. Sabbir MG, Wigle N, Loewen S, Gu Y, Buse C, Hicks GG et al. (2010). Identification and characterization of Dlc1 isoforms in the mouse and study of the biological function of a single gene trapped isoform. BMC Biology 8: 17.
45. Sekimata M, Kabuyama Y, Emori Y, Homma Y. (1999). Morphological changes and detachment of adherent cells induced by p122, a GTPase-activating protein for Rho. J Biol Chem 274: 17757-17762.
46. Seng TJ, Low JSW, Li H, Cui Y, Goh HK, Wong MLY et al. (2007). 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 26: 934-944.
47. Small IF, Peeters NF, Legeai FF, Lurin C. (2004). Predotar: a tool for rapidly screening proteomes for N-terminal targeting sequences. PROTEOMICS 4: 1581-1590. (Pubitemid 38738317)
48. Takai D, Jones PA. (2002). Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci USA 99: 3740-3745. (Pubitemid 34252176)
49. Takai D, Jones PA. (2003). The CpG island searcher: a new WWW resource. In Silico Biol 3: 235-240. (Pubitemid 37493047)
50. Tao Q, Huang H, Geiman TM, Lim CY, Fu L, Qiu GH et al. (2002). Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells. Hum Mol Genet 11: 2091-2102. (Pubitemid 34993997)
51. Tao Q, Robertson KD, Manns A, Hildesheim A, Ambinder RF. (1998). Epstein-Barr virus (EBV) in endemic Burkitt's lymphoma: molecular analysis of primary tumor tissue. Blood 91: 1373-1381. (Pubitemid 28086891)
52. Tao Q, Swinnen LJ, Yang J, Srivastava G, Robertson KD, Ambinder RF. (1999). 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 155: 619-625. (Pubitemid 29370411)
53. Tcherkezian J, Lamarche-Vane N. (2007). Current knowledge of the large RhoGAP family of proteins. Biol Cell 99: 67-86. (Pubitemid 46242033)
54. Tsao SW, Wang X, Liu Y, Cheung YC, Feng H, Zheng Z et al. (2002). Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40 large T and HPV16E6/E7 viral oncogenes. Biochim Biophys Acta 1590: 150-158. (Pubitemid 34626778)
55. Wong CM, Lee JM, Ching YP, Jin DY, Ng IO. (2003). Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Cancer Res 63: 7646-7651. (Pubitemid 37466690)
56. Xu CF, Brown MA, Chambers JA, Griffiths B, Nicolai H, Solomon E. (1995). Distinct transcription start sites generate two forms of BRCA1 mRNA. Hum Mol Genet 4: 2259-2264.
57. Xue W, Krasnitz A, Lucito R, Sordella R, VanAelst L, Cordon-Cardo C et al. (2008). The ITGB2 immunomodulatory gene (CD18), enterocolitis, and Hirschsprung's disease. Genes & Development 22: 1439-1444.
58. Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao SW et al. (2005a). Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene 25: 1070-1080. (Pubitemid 43277014)
59. Ying J, Srivastava G, Hsieh WS, Gao Z, Murray P, Liao SK et al. (2005b). 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 11: 6442-6449. (Pubitemid 41338980)
60. Yuan BZ, Durkin ME, Popescu NC. (2003). Promoter hypermethyla-tion of DLC-1, a candidate tumor suppressor gene, in several common human cancers. Cancer Genet Cytogenet 140: 113-117. (Pubitemid 36349010)
61. Yuan BZ, Jefferson AM, Baldwin KT, Thorgeirsson SS, Popescu NC, Reynolds SH. (2004). DLC-1 operates as a tumor suppressor gene in human non-small cell lung carcinomas. Oncogene 23: 1405-1411. (Pubitemid 38406835)
62. Yuan BZ, Jefferson AM, Millecchia L, Popescu NC, Reynolds SH. (2007). Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells. Exp Cell Res 313: 3868-3880. (Pubitemid 47561896)
63. Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC. (1998). Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer Res 58: 2196-2199. (Pubitemid 28232908)
64. Zhou X, Thorgeirsson SS, Popescu NC. (2004). Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells. Oncogene 23: 1308-1313. (Pubitemid 38297186)
65. Zhou X, Wang XW, Xu L, Hagiwara K, Nagashima M, Wolkowicz R et al. (1999). COOH-terminal domain of p53 modulates p53-mediated transcriptional transactivation, cell growth, and apoptosis. Cancer Res 59: 843-848. (Pubitemid 29086737)