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Published in: Molecular Cancer 1/2015

Open Access 01-12-2015 | Review

DDX3, a potential target for cancer treatment

Authors: Guus Martinus Bol, Min Xie, Venu Raman

Published in: Molecular Cancer | Issue 1/2015

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Abstract

RNA helicases are a large family of proteins with a distinct motif, referred to as the DEAD/H (Asp-Glu-Ala-Asp/His). The exact functions of all the human DEAD/H box proteins are unknown. However, it has been consistently demonstrated that these proteins are associated with several aspects of energy-dependent RNA metabolism, including translation, ribosome biogenesis, and pre-mRNA splicing. In addition, DEAD/H box proteins participate in nuclear-cytoplasmic transport and organellar gene expression.
A member of this RNA helicase family, DDX3, has been identified in a variety of cellular biogenesis processes, including cell-cycle regulation, cellular differentiation, cell survival, and apoptosis. In cancer, DDX3 expression has been evaluated in patient samples of breast, lung, colon, oral, and liver cancer. Both tumor suppressor and oncogenic functions have been attributed to DDX3 and are discussed in this review. In general, there is concordance with in vitro evidence to support the hypothesis that DDX3 is associated with an aggressive phenotype in human malignancies. Interestingly, very few cancer types harbor mutations in DDX3, which result in altered protein function rather than a loss of function.
Efficacy of drugs to curtail cancer growth is hindered by adaptive responses that promote drug resistance, eventually leading to treatment failure. One way to circumvent development of resistant disease is to develop novel drugs that target over-expressed proteins involved in this adaptive response. Moreover, if the target gene is developmentally regulated, there is less of a possibility to abruptly accumulate mutations leading to drug resistance. In this regard, DDX3 could be a druggable target for cancer treatment. We present an overview of DDX3 biology and the currently available DDX3 inhibitors for cancer treatment.
Literature
1.
2.
go back to reference Soto-Rifo R, Ohlmann T. The role of the DEAD-box RNA helicase DDX3 in mRNA metabolism. Wiley Interdiscip Rev RNA. 2013;4:369–85.CrossRefPubMed Soto-Rifo R, Ohlmann T. The role of the DEAD-box RNA helicase DDX3 in mRNA metabolism. Wiley Interdiscip Rev RNA. 2013;4:369–85.CrossRefPubMed
3.
go back to reference Kwong AD, Rao BG, Jeang KT. Viral and cellular RNA helicases as antiviral targets. Nat Rev Drug Discov. 2005;4:845–53.CrossRefPubMed Kwong AD, Rao BG, Jeang KT. Viral and cellular RNA helicases as antiviral targets. Nat Rev Drug Discov. 2005;4:845–53.CrossRefPubMed
4.
go back to reference Li Q, Zhang P, Zhang C, Wang Y, Wan R, Yang Y, et al. DDX3X regulates cell survival and cell cycle during mouse early embryonic development. J Biomed Res. 2014;28:282–91. Li Q, Zhang P, Zhang C, Wang Y, Wan R, Yang Y, et al. DDX3X regulates cell survival and cell cycle during mouse early embryonic development. J Biomed Res. 2014;28:282–91.
6.
go back to reference Kim YS, Lee SG, Park SH, Song K. Gene structure of the human DDX3 and chromosome mapping of its related sequences. Mol Cells. 2001;12:209–14.PubMed Kim YS, Lee SG, Park SH, Song K. Gene structure of the human DDX3 and chromosome mapping of its related sequences. Mol Cells. 2001;12:209–14.PubMed
7.
go back to reference Foresta C, Ferlin A, Moro E. Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility. Hum Mol Genet. 2000;9:1161–9.CrossRefPubMed Foresta C, Ferlin A, Moro E. Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility. Hum Mol Genet. 2000;9:1161–9.CrossRefPubMed
8.
go back to reference Ditton HJ, Zimmer J, Kamp C, Rajpert-De Meyts E, Vogt PH. The AZFa gene DBY (DDX3Y) is widely transcribed but the protein is limited to the male germ cells by translation control. Hum Mol Genet. 2004;13:2333–41.CrossRefPubMed Ditton HJ, Zimmer J, Kamp C, Rajpert-De Meyts E, Vogt PH. The AZFa gene DBY (DDX3Y) is widely transcribed but the protein is limited to the male germ cells by translation control. Hum Mol Genet. 2004;13:2333–41.CrossRefPubMed
9.
go back to reference Park SH, Lee SG, Kim Y, Song K. Assignment of a human putative RNA helicase gene, DDX3, to human X chromosome bands p11.3 > p11.23. Cytogenet Cell Genet. 1998;81:178–9.CrossRefPubMed Park SH, Lee SG, Kim Y, Song K. Assignment of a human putative RNA helicase gene, DDX3, to human X chromosome bands p11.3 > p11.23. Cytogenet Cell Genet. 1998;81:178–9.CrossRefPubMed
10.
go back to reference Mamiya N, Worman HJ. Hepatitis C virus core protein binds to a DEAD box RNA helicase. J Biol Chem. 1999;274:15751–6.CrossRefPubMed Mamiya N, Worman HJ. Hepatitis C virus core protein binds to a DEAD box RNA helicase. J Biol Chem. 1999;274:15751–6.CrossRefPubMed
11.
go back to reference Johnstone O, Deuring R, Bock R, Linder P, Fuller MT, Lasko P. Belle is a Drosophila DEAD-box protein required for viability and in the germ line. Dev Biol. 2005;277:92–101.CrossRefPubMed Johnstone O, Deuring R, Bock R, Linder P, Fuller MT, Lasko P. Belle is a Drosophila DEAD-box protein required for viability and in the germ line. Dev Biol. 2005;277:92–101.CrossRefPubMed
13.
go back to reference Liu WS, Wang A, Yang Y, Chang TC, Landrito E, Yasue H. Molecular characterization of the DDX3Y gene and its homologs in cattle. Cytogenet Genome Res. 2009;126:318–28.CrossRefPubMed Liu WS, Wang A, Yang Y, Chang TC, Landrito E, Yasue H. Molecular characterization of the DDX3Y gene and its homologs in cattle. Cytogenet Genome Res. 2009;126:318–28.CrossRefPubMed
14.
go back to reference Vong QP, Li Y, Lau YF, Dym M, Rennert OM, Chan WY. Structural characterization and expression studies of Dby and its homologs in the mouse. J Androl. 2006;27:653–61.CrossRefPubMed Vong QP, Li Y, Lau YF, Dym M, Rennert OM, Chan WY. Structural characterization and expression studies of Dby and its homologs in the mouse. J Androl. 2006;27:653–61.CrossRefPubMed
15.
go back to reference Fullam A, Schroder M. DExD/H-box RNA helicases as mediators of anti-viral innate immunity and essential host factors for viral replication. Biochim Biophys Acta. 1829;2013:854–65. Fullam A, Schroder M. DExD/H-box RNA helicases as mediators of anti-viral innate immunity and essential host factors for viral replication. Biochim Biophys Acta. 1829;2013:854–65.
16.
go back to reference Rodamilans B, Montoya G. Expression, purification, crystallization and preliminary X-ray diffraction analysis of the DDX3 RNA helicase domain. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:283–6.PubMedCentralCrossRefPubMed Rodamilans B, Montoya G. Expression, purification, crystallization and preliminary X-ray diffraction analysis of the DDX3 RNA helicase domain. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:283–6.PubMedCentralCrossRefPubMed
17.
go back to reference Hogbom M, Collins R, van den Berg S, Jenvert RM, Karlberg T, Kotenyova T, et al. Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP. J Mol Biol. 2007;372:150–9. Hogbom M, Collins R, van den Berg S, Jenvert RM, Karlberg T, Kotenyova T, et al. Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP. J Mol Biol. 2007;372:150–9.
18.
go back to reference Shi H, Cordin O, Minder CM, Linder P, Xu RM. Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A. 2004;101:17628–33.PubMedCentralCrossRefPubMed Shi H, Cordin O, Minder CM, Linder P, Xu RM. Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A. 2004;101:17628–33.PubMedCentralCrossRefPubMed
19.
go back to reference Franca R, Belfiore A, Spadari S, Maga G. Human DEAD-Box ATPase DDX3 shows a relaxed nucleoside substrate specificity. Proteins-Structure Function Bioinform. 2007;67:1128–37.CrossRef Franca R, Belfiore A, Spadari S, Maga G. Human DEAD-Box ATPase DDX3 shows a relaxed nucleoside substrate specificity. Proteins-Structure Function Bioinform. 2007;67:1128–37.CrossRef
20.
go back to reference Epling LB, Grace CR, Lowe BR, Partridge JF, Enemark EJ. Cancer-Associated Mutants of RNA Helicase DDX3X Are Defective in RNA-Stimulated ATP Hydrolysis. J Mol Biol. 2015;427:1779–96.CrossRefPubMed Epling LB, Grace CR, Lowe BR, Partridge JF, Enemark EJ. Cancer-Associated Mutants of RNA Helicase DDX3X Are Defective in RNA-Stimulated ATP Hydrolysis. J Mol Biol. 2015;427:1779–96.CrossRefPubMed
21.
go back to reference Sengoku T, Nureki O, Nakamura A, Kobayashi S, Yokoyama S. Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa. Cell. 2006;125:287–300.CrossRefPubMed Sengoku T, Nureki O, Nakamura A, Kobayashi S, Yokoyama S. Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa. Cell. 2006;125:287–300.CrossRefPubMed
22.
go back to reference Sharma D, Jankowsky E. The Ded1/DDX3 subfamily of DEAD-box RNA helicases. Crit Rev Biochem Mol Biol. 2014;49:343–60.CrossRefPubMed Sharma D, Jankowsky E. The Ded1/DDX3 subfamily of DEAD-box RNA helicases. Crit Rev Biochem Mol Biol. 2014;49:343–60.CrossRefPubMed
23.
go back to reference Botlagunta M, Vesuna F, Mironchik Y, Raman A, Lisok A, Winnard Jr P, et al. Oncogenic role of DDX3 in breast cancer biogenesis. Oncogene. 2008;27:3912–22. Botlagunta M, Vesuna F, Mironchik Y, Raman A, Lisok A, Winnard Jr P, et al. Oncogenic role of DDX3 in breast cancer biogenesis. Oncogene. 2008;27:3912–22.
24.
go back to reference Chao CH, Chen CM, Cheng PL, Shih JW, Tsou AP, Lee YH. DDX3, a DEAD box RNA helicase with tumor growth-suppressive property and transcriptional regulation activity of the p21waf1/cip1 promoter, is a candidate tumor suppressor. Cancer Res. 2006;66:6579–88.CrossRefPubMed Chao CH, Chen CM, Cheng PL, Shih JW, Tsou AP, Lee YH. DDX3, a DEAD box RNA helicase with tumor growth-suppressive property and transcriptional regulation activity of the p21waf1/cip1 promoter, is a candidate tumor suppressor. Cancer Res. 2006;66:6579–88.CrossRefPubMed
25.
go back to reference Schroder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J. 2008;27:2147–57.PubMedCentralCrossRefPubMed Schroder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J. 2008;27:2147–57.PubMedCentralCrossRefPubMed
26.
go back to reference Merz C, Urlaub H, Will CL, Luhrmann R. Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment. RNA. 2007;13:116–28.PubMedCentralCrossRefPubMed Merz C, Urlaub H, Will CL, Luhrmann R. Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment. RNA. 2007;13:116–28.PubMedCentralCrossRefPubMed
27.
go back to reference Yedavalli VS, Neuveut C, Chi YH, Kleiman L, Jeang KT. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell. 2004;119:381–92.CrossRefPubMed Yedavalli VS, Neuveut C, Chi YH, Kleiman L, Jeang KT. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell. 2004;119:381–92.CrossRefPubMed
28.
go back to reference Lai MC, Lee YH, Tarn WY. The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control. Mol Biol Cell. 2008;19:3847–58.PubMedCentralCrossRefPubMed Lai MC, Lee YH, Tarn WY. The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control. Mol Biol Cell. 2008;19:3847–58.PubMedCentralCrossRefPubMed
29.
go back to reference Geissler R, Golbik RP, Behrens SE. The DEAD-box helicase DDX3 supports the assembly of functional 80S ribosomes. Nucleic Acids Res. 2012;40:4998–5011.PubMedCentralCrossRefPubMed Geissler R, Golbik RP, Behrens SE. The DEAD-box helicase DDX3 supports the assembly of functional 80S ribosomes. Nucleic Acids Res. 2012;40:4998–5011.PubMedCentralCrossRefPubMed
30.
go back to reference Lee CS, Dias AP, Jedrychowski M, Patel AH, Hsu JL, Reed R. Human DDX3 functions in translation and interacts with the translation initiation factor eIF3. Nucleic Acids Res. 2008;36:4708–18.PubMedCentralCrossRefPubMed Lee CS, Dias AP, Jedrychowski M, Patel AH, Hsu JL, Reed R. Human DDX3 functions in translation and interacts with the translation initiation factor eIF3. Nucleic Acids Res. 2008;36:4708–18.PubMedCentralCrossRefPubMed
31.
go back to reference Soto-Rifo R, Rubilar PS, Limousin T, de Breyne S, Decimo D, Ohlmann T. DEAD-box protein DDX3 associates with eIF4F to promote translation of selected mRNAs. EMBO J. 2012;31:3745–56.PubMedCentralCrossRefPubMed Soto-Rifo R, Rubilar PS, Limousin T, de Breyne S, Decimo D, Ohlmann T. DEAD-box protein DDX3 associates with eIF4F to promote translation of selected mRNAs. EMBO J. 2012;31:3745–56.PubMedCentralCrossRefPubMed
32.
go back to reference Fukumura J, Noguchi E, Sekiguchi T, Nishimoto T. A temperature-sensitive mutant of the mammalian RNA helicase, DEAD-BOX X isoform, DBX, defective in the transition from G1 to S phase. J Biochem. 2003;134:71–82.CrossRefPubMed Fukumura J, Noguchi E, Sekiguchi T, Nishimoto T. A temperature-sensitive mutant of the mammalian RNA helicase, DEAD-BOX X isoform, DBX, defective in the transition from G1 to S phase. J Biochem. 2003;134:71–82.CrossRefPubMed
33.
go back to reference Shih JW, Wang WT, Tsai TY, Kuo CY, Li HK, Wu Lee YH. Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response. Biochem J. 2012;441:119–29.CrossRefPubMed Shih JW, Wang WT, Tsai TY, Kuo CY, Li HK, Wu Lee YH. Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response. Biochem J. 2012;441:119–29.CrossRefPubMed
34.
go back to reference Celik H, Sajwan KP, Selvanathan SP, Marsh BJ, Pai AV, Kont YS, et al. Ezrin Binds to DEAD-Box RNA Helicase DDX3 and Regulates Its Function and Protein Level. Mol Cell Biol. 2015;35:3145–62. Celik H, Sajwan KP, Selvanathan SP, Marsh BJ, Pai AV, Kont YS, et al. Ezrin Binds to DEAD-Box RNA Helicase DDX3 and Regulates Its Function and Protein Level. Mol Cell Biol. 2015;35:3145–62.
35.
37.
go back to reference Kwon S, Zhang Y, Matthias P. The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev. 2007;21:3381–94.PubMedCentralCrossRefPubMed Kwon S, Zhang Y, Matthias P. The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev. 2007;21:3381–94.PubMedCentralCrossRefPubMed
38.
go back to reference Eisinger-Mathason TS, Andrade J, Groehler AL, Clark DE, Muratore-Schroeder TL, Pasic L, et al. Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival. Mol Cell. 2008;31:722–36. Eisinger-Mathason TS, Andrade J, Groehler AL, Clark DE, Muratore-Schroeder TL, Pasic L, et al. Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival. Mol Cell. 2008;31:722–36.
39.
go back to reference Anderson P, Kedersha N. Stress granules: the Tao of RNA triage. Trends Biochem Sci. 2008;33:141–50.CrossRefPubMed Anderson P, Kedersha N. Stress granules: the Tao of RNA triage. Trends Biochem Sci. 2008;33:141–50.CrossRefPubMed
40.
go back to reference Hilliker A, Gao Z, Jankowsky E, Parker R. The DEAD-box protein Ded1 modulates translation by the formation and resolution of an eIF4F-mRNA complex. Mol Cell. 2011;43:962–72.PubMedCentralCrossRefPubMed Hilliker A, Gao Z, Jankowsky E, Parker R. The DEAD-box protein Ded1 modulates translation by the formation and resolution of an eIF4F-mRNA complex. Mol Cell. 2011;43:962–72.PubMedCentralCrossRefPubMed
41.
go back to reference Beckham C, Hilliker A, Cziko AM, Noueiry A, Ramaswami M, Parker R. The DEAD-box RNA helicase Ded1p affects and accumulates in Saccharomyces cerevisiae P-bodies. Mol Biol Cell. 2008;19:984–93.PubMedCentralCrossRefPubMed Beckham C, Hilliker A, Cziko AM, Noueiry A, Ramaswami M, Parker R. The DEAD-box RNA helicase Ded1p affects and accumulates in Saccharomyces cerevisiae P-bodies. Mol Biol Cell. 2008;19:984–93.PubMedCentralCrossRefPubMed
43.
go back to reference Grousl T, Ivanov P, Frydlova I, Vasicova P, Janda F, Vojtova J, et al. Robust heat shock induces eIF2alpha-phosphorylation-independent assembly of stress granules containing eIF3 and 40S ribosomal subunits in budding yeast, Saccharomyces cerevisiae. J Cell Sci. 2009;122:2078–88. Grousl T, Ivanov P, Frydlova I, Vasicova P, Janda F, Vojtova J, et al. Robust heat shock induces eIF2alpha-phosphorylation-independent assembly of stress granules containing eIF3 and 40S ribosomal subunits in budding yeast, Saccharomyces cerevisiae. J Cell Sci. 2009;122:2078–88.
44.
go back to reference Sun M, Zhou T, Jonasch E, Jope RS. DDX3 regulates DNA damage-induced apoptosis and p53 stabilization. Biochim Biophys Acta. 1833;2013:1489–97. Sun M, Zhou T, Jonasch E, Jope RS. DDX3 regulates DNA damage-induced apoptosis and p53 stabilization. Biochim Biophys Acta. 1833;2013:1489–97.
45.
go back to reference Bol GM, Raman V, van der Groep P, Vermeulen JF, Patel AH, van der Wall E, et al. Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer. PLoS One. 2013;8:e63548. Bol GM, Raman V, van der Groep P, Vermeulen JF, Patel AH, van der Wall E, et al. Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer. PLoS One. 2013;8:e63548.
46.
go back to reference Botlagunta M, Krishnamachary B, Vesuna F, Winnard Jr PT, Bol GM, Patel AH, et al. Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells. PLoS One. 2011;6:e17563. Botlagunta M, Krishnamachary B, Vesuna F, Winnard Jr PT, Bol GM, Patel AH, et al. Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells. PLoS One. 2011;6:e17563.
47.
go back to reference Bol GM, Vesuna F, Xie M, Zeng J, Aziz K, Gandhi N, et al. Targeting DDX3 with a small molecule inhibitor for lung cancer therapy. EMBO Mol Med. 2015;7:648–69. Bol GM, Vesuna F, Xie M, Zeng J, Aziz K, Gandhi N, et al. Targeting DDX3 with a small molecule inhibitor for lung cancer therapy. EMBO Mol Med. 2015;7:648–69.
48.
go back to reference Brown JM, Giaccia AJ. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 1998;58:1408–16.PubMed Brown JM, Giaccia AJ. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 1998;58:1408–16.PubMed
49.
go back to reference Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989;49:6449–65.PubMed Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989;49:6449–65.PubMed
50.
go back to reference Semenza GL. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol. 2000;35:71–103.CrossRefPubMed Semenza GL. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol. 2000;35:71–103.CrossRefPubMed
52.
53.
go back to reference Li Y, Wang H, Wang Z, Makhija S, Buchsbaum D, LoBuglio A, et al. Inducible resistance of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand receptor 2-mediated apoptosis by generation of a blockade at the death domain function. Cancer Res. 2006;66:8520–8. Li Y, Wang H, Wang Z, Makhija S, Buchsbaum D, LoBuglio A, et al. Inducible resistance of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand receptor 2-mediated apoptosis by generation of a blockade at the death domain function. Cancer Res. 2006;66:8520–8.
54.
go back to reference Chang DW, Xing Z, Pan Y, Algeciras-Schimnich A, Barnhart BC, Yaish-Ohad S, et al. c-FLIPL is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J. 2002;21:3704–14. Chang DW, Xing Z, Pan Y, Algeciras-Schimnich A, Barnhart BC, Yaish-Ohad S, et al. c-FLIPL is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J. 2002;21:3704–14.
55.
go back to reference Shu HB, Takeuchi M, Goeddel DV. The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proc Natl Acad Sci U S A. 1996;93:13973–8.PubMedCentralCrossRefPubMed Shu HB, Takeuchi M, Goeddel DV. The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proc Natl Acad Sci U S A. 1996;93:13973–8.PubMedCentralCrossRefPubMed
56.
go back to reference Beurel E, Jope RS. The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Prog Neurobiol. 2006;79:173–89.PubMedCentralCrossRefPubMed Beurel E, Jope RS. The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Prog Neurobiol. 2006;79:173–89.PubMedCentralCrossRefPubMed
57.
58.
go back to reference Oliver PG, LoBuglio AF, Zhou T, Forero A, Kim H, Zinn KR, et al. Effect of anti-DR5 and chemotherapy on basal-like breast cancer. Breast Cancer Res Treat. 2012;133:417–26. Oliver PG, LoBuglio AF, Zhou T, Forero A, Kim H, Zinn KR, et al. Effect of anti-DR5 and chemotherapy on basal-like breast cancer. Breast Cancer Res Treat. 2012;133:417–26.
59.
go back to reference Wu DW, Liu WS, Wang J, Chen CY, Cheng YW, Lee H. Reduced p21(WAF1/CIP1) via alteration of p53-DDX3 pathway is associated with poor relapse-free survival in early-stage human papillomavirus-associated lung cancer. Clin Cancer Res. 2011;17:1895–905.CrossRefPubMed Wu DW, Liu WS, Wang J, Chen CY, Cheng YW, Lee H. Reduced p21(WAF1/CIP1) via alteration of p53-DDX3 pathway is associated with poor relapse-free survival in early-stage human papillomavirus-associated lung cancer. Clin Cancer Res. 2011;17:1895–905.CrossRefPubMed
60.
go back to reference Choi YJ, Kang LJ, Lee SG. Stimulation of DDX3 expression by ginsenoside Rg3 through the Akt/p53 pathway activates the innate immune response via TBK1/IKKepsilon/IRF3 signalling. Curr Med Chem. 2014;21:1050–60.CrossRefPubMed Choi YJ, Kang LJ, Lee SG. Stimulation of DDX3 expression by ginsenoside Rg3 through the Akt/p53 pathway activates the innate immune response via TBK1/IKKepsilon/IRF3 signalling. Curr Med Chem. 2014;21:1050–60.CrossRefPubMed
62.
go back to reference Hoe KK, Verma CS, Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov. 2014;13:217–36.CrossRefPubMed Hoe KK, Verma CS, Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov. 2014;13:217–36.CrossRefPubMed
64.
go back to reference Kondaskar A, Kondaskar S, Kumar R, Fishbein JC, Muvarak N, Lapidus RG, et al. Novel, Broad Spectrum Anti-Cancer Agents Containing the Tricyclic 5:7:5-Fused Diimidazodiazepine Ring System. ACS Med Chem Lett. 2010;2:252–6. Kondaskar A, Kondaskar S, Kumar R, Fishbein JC, Muvarak N, Lapidus RG, et al. Novel, Broad Spectrum Anti-Cancer Agents Containing the Tricyclic 5:7:5-Fused Diimidazodiazepine Ring System. ACS Med Chem Lett. 2010;2:252–6.
65.
go back to reference Huang JS, Chao CC, Su TL, Yeh SH, Chen DS, Chen CT, et al. Diverse cellular transformation capability of overexpressed genes in human hepatocellular carcinoma. Biochem Biophys Res Commun. 2004;315:950–8. Huang JS, Chao CC, Su TL, Yeh SH, Chen DS, Chen CT, et al. Diverse cellular transformation capability of overexpressed genes in human hepatocellular carcinoma. Biochem Biophys Res Commun. 2004;315:950–8.
66.
go back to reference Sekiguchi T, Kurihara Y, Fukumura J. Phosphorylation of threonine 204 of DEAD-box RNA helicase DDX3 by cyclin B/cdc2 in vitro. Biochem Biophys Res Commun. 2007;356:668–73.CrossRefPubMed Sekiguchi T, Kurihara Y, Fukumura J. Phosphorylation of threonine 204 of DEAD-box RNA helicase DDX3 by cyclin B/cdc2 in vitro. Biochem Biophys Res Commun. 2007;356:668–73.CrossRefPubMed
67.
go back to reference Grallert B, Kearsey SE, Lenhard M, Carlson CR, Nurse P, Boye E, et al. A fission yeast general translation factor reveals links between protein synthesis and cell cycle controls. J Cell Sci. 2000;113:1447–58. Grallert B, Kearsey SE, Lenhard M, Carlson CR, Nurse P, Boye E, et al. A fission yeast general translation factor reveals links between protein synthesis and cell cycle controls. J Cell Sci. 2000;113:1447–58.
68.
go back to reference Chang PC, Chi CW, Chau GY, Li FY, Tsai YH, Wu JC, et al. DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control. Oncogene. 2006;25:1991–2003. Chang PC, Chi CW, Chau GY, Li FY, Tsai YH, Wu JC, et al. DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control. Oncogene. 2006;25:1991–2003.
69.
go back to reference Shih JW, Tsai TY, Chao CH, Wu Lee YH. Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein. Oncogene. 2008;27:700–14.CrossRefPubMed Shih JW, Tsai TY, Chao CH, Wu Lee YH. Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein. Oncogene. 2008;27:700–14.CrossRefPubMed
71.
go back to reference Yang L, Lin C, Liu ZR. P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin. Cell. 2006;127:139–55.CrossRefPubMed Yang L, Lin C, Liu ZR. P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin. Cell. 2006;127:139–55.CrossRefPubMed
72.
go back to reference Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature. 2012;488:106–10. Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature. 2012;488:106–10.
73.
go back to reference Cruciat CM, Dolde C, de Groot RE, Ohkawara B, Reinhard C, Korswagen HC, et al. RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-beta-catenin signaling. Science. 2013;339:1436–41. Cruciat CM, Dolde C, de Groot RE, Ohkawara B, Reinhard C, Korswagen HC, et al. RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-beta-catenin signaling. Science. 2013;339:1436–41.
74.
go back to reference Chen HH, Yu HI, Cho WC, Tarn WY. DDX3 modulates cell adhesion and motility and cancer cell metastasis via Rac1-mediated signaling pathway. Oncogene. 2015;34:2790–800.CrossRefPubMed Chen HH, Yu HI, Cho WC, Tarn WY. DDX3 modulates cell adhesion and motility and cancer cell metastasis via Rac1-mediated signaling pathway. Oncogene. 2015;34:2790–800.CrossRefPubMed
75.
go back to reference Sun M, Song L, Zhou T, Gillespie GY, Jope RS. The role of DDX3 in regulating Snail. Biochim Biophys Acta. 1813;2011:438–47. Sun M, Song L, Zhou T, Gillespie GY, Jope RS. The role of DDX3 in regulating Snail. Biochim Biophys Acta. 1813;2011:438–47.
76.
go back to reference Wu DW, Lee MC, Wang J, Chen CY, Cheng YW, Lee H. DDX3 loss by p53 inactivation promotes tumor malignancy via the MDM2/Slug/E-cadherin pathway and poor patient outcome in non-small-cell lung cancer. Oncogene. 2014;33:1515–26.CrossRefPubMed Wu DW, Lee MC, Wang J, Chen CY, Cheng YW, Lee H. DDX3 loss by p53 inactivation promotes tumor malignancy via the MDM2/Slug/E-cadherin pathway and poor patient outcome in non-small-cell lung cancer. Oncogene. 2014;33:1515–26.CrossRefPubMed
77.
go back to reference Lee CH, Lin SH, Yang SF, Yang SM, Chen MK, Lee H, et al. Low/negative expression of DDX3 might predict poor prognosis in non-smoker patients with oral cancer. Oral Dis. 2014;20:76–83. Lee CH, Lin SH, Yang SF, Yang SM, Chen MK, Lee H, et al. Low/negative expression of DDX3 might predict poor prognosis in non-smoker patients with oral cancer. Oral Dis. 2014;20:76–83.
78.
go back to reference van Voss MR H, van Kempen PM, Noorlag R, van Diest PJ, Willems SM, Raman V. DDX3 has divergent roles in head and neck squamous cell carcinomas in smoking versus non-smoking patients. Oral Dis. 2015;21:270–1.CrossRef van Voss MR H, van Kempen PM, Noorlag R, van Diest PJ, Willems SM, Raman V. DDX3 has divergent roles in head and neck squamous cell carcinomas in smoking versus non-smoking patients. Oral Dis. 2015;21:270–1.CrossRef
79.
go back to reference Su CY, Lin TC, Lin YF, Chen MH, Lee CH, Wang HY, et al. DDX3 as a strongest prognosis marker and its downregulation promotes metastasis in colorectal cancer. Oncotarget. 2015;6:18602–12. Su CY, Lin TC, Lin YF, Chen MH, Lee CH, Wang HY, et al. DDX3 as a strongest prognosis marker and its downregulation promotes metastasis in colorectal cancer. Oncotarget. 2015;6:18602–12.
80.
81.
go back to reference Miao X, Yang ZL, Xiong L, Zou Q, Yuan Y, Li J, et al. Nectin-2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder. Int J Clin Exp Pathol. 2013;6:179–90. Miao X, Yang ZL, Xiong L, Zou Q, Yuan Y, Li J, et al. Nectin-2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder. Int J Clin Exp Pathol. 2013;6:179–90.
82.
go back to reference Xie M, Vesuna F, Botlagunta M, Bol GM, Irving A, Bergman Y et al. NZ51, a ring-expanded nucleoside analog, inhibits motility and viability of breast cancer cells by targeting the RNA helicase DDX3. Oncotarget 2015 Xie M, Vesuna F, Botlagunta M, Bol GM, Irving A, Bergman Y et al. NZ51, a ring-expanded nucleoside analog, inhibits motility and viability of breast cancer cells by targeting the RNA helicase DDX3. Oncotarget 2015
83.
go back to reference Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 2002;3:155–66.CrossRefPubMed Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 2002;3:155–66.CrossRefPubMed
84.
go back to reference Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333:1157–60. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333:1157–60.
85.
go back to reference Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011;365:2497–506. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011;365:2497–506.
86.
go back to reference Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123:465–72. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123:465–72.
87.
go back to reference Northcott PA, Jones DT, Kool M, Robinson GW, Gilbertson RJ, Cho YJ, et al. Medulloblastomics: the end of the beginning. Nat Rev Cancer. 2012;12:818–34. Northcott PA, Jones DT, Kool M, Robinson GW, Gilbertson RJ, Cho YJ, et al. Medulloblastomics: the end of the beginning. Nat Rev Cancer. 2012;12:818–34.
88.
go back to reference Jones DT, Jager N, Kool M, Zichner T, Hutter B, Sultan M, et al. Dissecting the genomic complexity underlying medulloblastoma. Nature. 2012;488:100–5. Jones DT, Jager N, Kool M, Zichner T, Hutter B, Sultan M, et al. Dissecting the genomic complexity underlying medulloblastoma. Nature. 2012;488:100–5.
89.
go back to reference Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, et al. Novel mutations target distinct subgroups of medulloblastoma. Nature. 2012;488:43–8. Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, et al. Novel mutations target distinct subgroups of medulloblastoma. Nature. 2012;488:43–8.
90.
go back to reference Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res. 2015;21:632–41. Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res. 2015;21:632–41.
91.
go back to reference India Project Team of the International Cancer Genome C. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun. 2013;4:2873. India Project Team of the International Cancer Genome C. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun. 2013;4:2873.
92.
go back to reference Heerma Van Voss M, Vesuna F, Trumpi K, Brilliant J, Berlinicke C, de Leng W, et al. Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer. Oncotarget. 2015;6:28312–26. Heerma Van Voss M, Vesuna F, Trumpi K, Brilliant J, Berlinicke C, de Leng W, et al. Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer. Oncotarget. 2015;6:28312–26.
93.
go back to reference Wilky BA, Kim C, McCarty G, Montgomery EA, Kammers K, DeVine LR et al. RNA helicase DDX3: a novel therapeutic target in Ewing sarcoma. Oncogene 2015, doi:10.1038/onc.2015.336. Wilky BA, Kim C, McCarty G, Montgomery EA, Kammers K, DeVine LR et al. RNA helicase DDX3: a novel therapeutic target in Ewing sarcoma. Oncogene 2015, doi:10.​1038/​onc.​2015.​336.
94.
go back to reference Jiang L, Gu ZH, Yan ZX, Zhao X, Xie YY, Zhang ZG, et al. Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma. Nat Genet. 2015;47:1061–6. Jiang L, Gu ZH, Yan ZX, Zhao X, Xie YY, Zhang ZG, et al. Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma. Nat Genet. 2015;47:1061–6.
95.
go back to reference Liang WS, Maddukuri A, Teslovich T, de la Fuente C, Agbottah E, Dadgar S, et al. Therapeutic targets for HIV-1 infection in the host proteome. Retrovirology. 2005;2:20. Liang WS, Maddukuri A, Teslovich T, de la Fuente C, Agbottah E, Dadgar S, et al. Therapeutic targets for HIV-1 infection in the host proteome. Retrovirology. 2005;2:20.
96.
go back to reference Yedavalli VS, Zhang N, Cai H, Zhang P, Starost MF, Hosmane RS, et al. Ring expanded nucleoside analogues inhibit RNA helicase and intracellular human immunodeficiency virus type 1 replication. J Med Chem. 2008;51:5043–51. Yedavalli VS, Zhang N, Cai H, Zhang P, Starost MF, Hosmane RS, et al. Ring expanded nucleoside analogues inhibit RNA helicase and intracellular human immunodeficiency virus type 1 replication. J Med Chem. 2008;51:5043–51.
97.
go back to reference Maga G, Falchi F, Garbelli A, Belfiore A, Witvrouw M, Manetti F, et al. Pharmacophore modeling and molecular docking led to the discovery of inhibitors of human immunodeficiency virus-1 replication targeting the human cellular aspartic acid-glutamic acid-alanine-aspartic acid box polypeptide 3. J Med Chem. 2008;51:6635–8. Maga G, Falchi F, Garbelli A, Belfiore A, Witvrouw M, Manetti F, et al. Pharmacophore modeling and molecular docking led to the discovery of inhibitors of human immunodeficiency virus-1 replication targeting the human cellular aspartic acid-glutamic acid-alanine-aspartic acid box polypeptide 3. J Med Chem. 2008;51:6635–8.
98.
go back to reference Maga G, Falchi F, Radi M, Botta L, Casaluce G, Bernardini M, et al. Toward the discovery of novel anti-HIV drugs. Second-generation inhibitors of the cellular ATPase DDX3 with improved anti-HIV activity: synthesis, structure-activity relationship analysis, cytotoxicity studies, and target validation. Chem Med Chem. 2011;6:1371–89. Maga G, Falchi F, Radi M, Botta L, Casaluce G, Bernardini M, et al. Toward the discovery of novel anti-HIV drugs. Second-generation inhibitors of the cellular ATPase DDX3 with improved anti-HIV activity: synthesis, structure-activity relationship analysis, cytotoxicity studies, and target validation. Chem Med Chem. 2011;6:1371–89.
99.
go back to reference Shadrick WR, Ndjomou J, Kolli R, Mukherjee S, Hanson AM, Frick DN. Discovering new medicines targeting helicases: challenges and recent progress. J Biomol Screen. 2013;18:761–81.PubMedCentralCrossRefPubMed Shadrick WR, Ndjomou J, Kolli R, Mukherjee S, Hanson AM, Frick DN. Discovering new medicines targeting helicases: challenges and recent progress. J Biomol Screen. 2013;18:761–81.PubMedCentralCrossRefPubMed
100.
go back to reference Kumar R, Ujjinamatada RK, Hosmane RS. The first synthesis of a novel 5:7:5-fused diimidazodiazepine ring system and some of its chemical properties. Org Lett. 2008;10:4681–4.PubMedCentralCrossRefPubMed Kumar R, Ujjinamatada RK, Hosmane RS. The first synthesis of a novel 5:7:5-fused diimidazodiazepine ring system and some of its chemical properties. Org Lett. 2008;10:4681–4.PubMedCentralCrossRefPubMed
101.
go back to reference Kondaskar A, Kondaskar S, Fishbein JC, Carter-Cooper BA, Lapidus RG, Sadowska M, et al. Structure-based drug design and potent anti-cancer activity of tricyclic 5:7:5-fused diimidazo[4,5-d:4',5'-f][1,3]diazepines. Bioorg Med Chem. 2013;21:618–31. Kondaskar A, Kondaskar S, Fishbein JC, Carter-Cooper BA, Lapidus RG, Sadowska M, et al. Structure-based drug design and potent anti-cancer activity of tricyclic 5:7:5-fused diimidazo[4,5-d:4',5'-f][1,3]diazepines. Bioorg Med Chem. 2013;21:618–31.
102.
go back to reference Garbelli A, Radi M, Falchi F, Beermann S, Zanoli S, Manetti F, et al. Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replication. Curr Med Chem. 2011;18:3015–27. Garbelli A, Radi M, Falchi F, Beermann S, Zanoli S, Manetti F, et al. Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replication. Curr Med Chem. 2011;18:3015–27.
103.
go back to reference Radi M, Falchi F, Garbelli A, Samuele A, Bernardo V, Paolucci S, et al. Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: towards the next generation HIV-1 inhibitors. Bioorg Med Chem Lett. 2012;22:2094–8. Radi M, Falchi F, Garbelli A, Samuele A, Bernardo V, Paolucci S, et al. Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: towards the next generation HIV-1 inhibitors. Bioorg Med Chem Lett. 2012;22:2094–8.
104.
go back to reference Samal SK, Routray S, Veeramachaneni GK, Dash R, Botlagunta M. Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer. Sci Rep. 2015;5:9982.PubMedCentralCrossRefPubMed Samal SK, Routray S, Veeramachaneni GK, Dash R, Botlagunta M. Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer. Sci Rep. 2015;5:9982.PubMedCentralCrossRefPubMed
105.
go back to reference La Thangue NB, Kerr DJ. Predictive biomarkers: a paradigm shift towards personalized cancer medicine. Nat Rev Clin Oncol. 2011;8:587–96.CrossRefPubMed La Thangue NB, Kerr DJ. Predictive biomarkers: a paradigm shift towards personalized cancer medicine. Nat Rev Clin Oncol. 2011;8:587–96.CrossRefPubMed
106.
go back to reference Fan CC, Lee LY, Yu MY, Tzen CY, Chou C, Chang MS. Upregulated hPuf-A promotes breast cancer tumorigenesis. Tumour Biol. 2013;34:2557–64.CrossRefPubMed Fan CC, Lee LY, Yu MY, Tzen CY, Chou C, Chang MS. Upregulated hPuf-A promotes breast cancer tumorigenesis. Tumour Biol. 2013;34:2557–64.CrossRefPubMed
107.
go back to reference Liu H, Zhang J, Wang S, Pang Z, Wang Z, Zhou W, et al. Screening of autoantibodies as potential biomarkers for hepatocellular carcinoma by using T7 phase display system. Cancer Epidemiol. 2012;36:82–8. Liu H, Zhang J, Wang S, Pang Z, Wang Z, Zhou W, et al. Screening of autoantibodies as potential biomarkers for hepatocellular carcinoma by using T7 phase display system. Cancer Epidemiol. 2012;36:82–8.
108.
go back to reference Zhao L, Li F, Taylor EW. Can tobacco use promote HCV-induced miR-122 hijacking and hepatocarcinogenesis? Med Hypotheses. 2013;80:131–3.CrossRefPubMed Zhao L, Li F, Taylor EW. Can tobacco use promote HCV-induced miR-122 hijacking and hepatocarcinogenesis? Med Hypotheses. 2013;80:131–3.CrossRefPubMed
109.
go back to reference Oveland E, Gjertsen BT, Wergeland L, Selheim F, Fladmark KE, Hovland R. Ligand-induced Flt3-downregulation modulates cell death associated proteins and enhances chemosensitivity to idarubicin in THP-1 acute myeloid leukemia cells. Leuk Res. 2009;33:276–87.CrossRefPubMed Oveland E, Gjertsen BT, Wergeland L, Selheim F, Fladmark KE, Hovland R. Ligand-induced Flt3-downregulation modulates cell death associated proteins and enhances chemosensitivity to idarubicin in THP-1 acute myeloid leukemia cells. Leuk Res. 2009;33:276–87.CrossRefPubMed
Metadata
Title
DDX3, a potential target for cancer treatment
Authors
Guus Martinus Bol
Min Xie
Venu Raman
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-015-0461-7

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