Skip to main content

Advertisement

SpringerLink
Log in

Twist: a molecular target in cancer therapeutics

  • Review
  • Published:
Tumor Biology

Abstract

Twist, the basic helix-loop-helix transcription factor, is involved in the process of epithelial to mesenchymal transitions (EMTs), which play an essential role in cancer metastasis. Overexpression of Twist or its promoter methylation is a common scenario in metastatic carcinomas. Twist is activated by a variety of signal transduction pathways, including Akt, signal transducer and activator of transcription 3, mitogen-activated protein kinase, Ras, and Wnt signaling. Activated Twist upregulates N-cadherin and downregulates E-cadherin, which are the hallmarks of EMT. Moreover, Twist plays an important role in some physiological processes involved in metastasis, like angiogenesis, invadopodia, extravasation, and chromosomal instability. Twist also protects cancer cells from apoptotic cell death. In addition, Twist is responsible for the stemness of cancer cells and the generation of drug resistance. Recently, targeting Twist has gained significant interests in cancer therapeutics. The inactivation of Twist by small RNA technology or chemotherapeutic approach has been proved successful. Moreover, several inhibitors which are antagonistic to the upstream or downstream molecules of Twist signaling pathways have also been identified. Development of potential treatment strategies by targeting Twist has a great promise in cancer therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kang Y, Massagué J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 2004;118:277–9.

    Article  CAS  PubMed  Google Scholar 

  2. Bourgeois P, Stoetzel C, Bolcato-Bellemin AL, Mattei MG, Perrin-Schmitt F. The human H-twist gene is located at 7p21 and encodes a B-HLH protein that is 96 % similar to its murine M-twist counterpart. Mamm Genome. 1996;7:915–7.

    Article  CAS  PubMed  Google Scholar 

  3. Howard TD, Paznekas WA, Green ED, Chiang LC, Ma N, Ortiz de Luna RI, et al. Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre–Chotzen syndrome. Nat Genet. 1997;15:36–41.

    Article  PubMed  Google Scholar 

  4. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.

    Article  CAS  PubMed  Google Scholar 

  5. Franco HL, Casasnovas J, Rodríguez-Medina JR, Cadilla CL. Redundant or separate entities?—roles of Twist1 and Twist2 as molecular switches during gene transcription. Nucleic Acids Res. 2011;39:1177–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Dunn B. Cancer: solving an age-old problem. Nature. 2012;483:S2–6.

    Article  CAS  PubMed  Google Scholar 

  7. Sahlin P, Windh P, Lauritzen C, Emanuelsson M, Grönberg H, Stenman G. Women with Saethre–Chotzen syndrome are at increased risk of breast cancer. Genes Chromosome Cancer. 2007;46:656–60.

    Article  CAS  Google Scholar 

  8. Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005;12:488–96.

    Article  PubMed  Google Scholar 

  9. Huang KT, Dobrovic A, Yan M, Karim RZ, Lee CS, Lakhani SR, et al. DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast. Breast Cancer Res Treat. 2010;124:555–65.

    Article  CAS  PubMed  Google Scholar 

  10. Vesuna F, Lisok A, Kimble B, Domek J, Kato Y, van der Groep P, et al. Twist contributes to hormone resistance in breast cancer by downregulating estrogen receptor-α. Oncogene. 2012;31:3223–34.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Fu J, Zhang L, He T, Xiao X, Liu X, Wang L, et al. TWIST represses estrogen receptor-alpha expression by recruiting the NuRD protein complex in breast cancer cells. Int J Biol Sci. 2012;8:522–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Hosono S, Kajiyama H, Terauchi M, Shibata K, Ino K, Nawa A, et al. Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients. Br J Cancer. 2007;96:314–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Shibata K, Kajiyama H, Ino K, Terauchi M, Yamamoto E, Nawa A, et al. Twist expression in patients with cervical cancer is associated with poor disease outcome. Ann Oncol. 2008;19:81–5.

    Article  CAS  PubMed  Google Scholar 

  14. Yuen HF, Chua CW, Chan YP, Wong YC, Wang X, Chan KW. Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer. Histopathology. 2007;50:648–58.

    Article  PubMed  Google Scholar 

  15. Yu Q, Zhang K, Wang X, Liu X, Zhang Z. Expression of transcription factors snail, slug, and twist in human bladder carcinoma. J Exp Clin Cancer Res. 2010;29:119.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. McConkey DJ, Choi W, Marquis L, Martin F, Williams MB, Shah J, et al. Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev. 2009;28:335–44.

    Article  CAS  PubMed  Google Scholar 

  17. Niu RF, Zhang L, Xi GM, Wei XY, Yang Y, Shi YR, et al. Up-regulation of Twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2007;26:385–94.

    CAS  PubMed  Google Scholar 

  18. Zhu Q, Xu H, Xu Q, Yan W, Tian D. Expression of Twist gene in human hepatocellular carcinoma cell strains of different metastatic potential. J Huazhong Univ Sci Technolog Med Sci. 2008;28:144–6.

    Article  CAS  PubMed  Google Scholar 

  19. Luo GQ, Li JH, Wen JF, Zhou YH, Hu YB, Zhou JH. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells. World J Gastroenterol. 2008;14:2487–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Okada T, Suehiro Y, Ueno K, Mitomori S, Kaneko S, Nishioka M, et al. TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer. Genes Chromosome Cancer. 2010;49:452–62.

    CAS  Google Scholar 

  21. Yuen HF, Chan YP, Wong ML, Kwok WK, Chan KK, Lee PY, et al. Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol. 2007;60:510–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Hotz B, Arndt M, Dullat S, Bhargava S, Buhr HJ, Hotz HG. Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer. Clin Cancer Res. 2007;13:4769–76.

    Article  CAS  PubMed  Google Scholar 

  23. Hung JJ, Yang MH, Hsu HS, Hsu WH, Liu JS, Wu KJ. Prognostic significance of hypoxia-inducible factor-1alpha, TWIST1 and Snail expression in resectable non-small cell lung cancer. Thorax. 2009;64:1082–9.

    Article  PubMed  Google Scholar 

  24. Song LB, Liao WT, Mai HQ, Zhang HZ, Zhang L, Li MZ, et al. The clinical significance of twist expression in nasopharyngeal carcinoma. Cancer Lett. 2006;242:258–65.

    Article  CAS  PubMed  Google Scholar 

  25. Elias MC, Tozer KR, Silber JR, Mikheeva S, Deng M, Morrison RS, et al. TWIST is expressed in human gliomas and promotes invasion. Neoplasia. 2005;7:824–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Miller SJ, Rangwala F, Williams J, Ackerman P, Kong S, Jegga AG, et al. Large-scale molecular comparison of human Schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues. Cancer Res. 2006;66:2584–91.

    Article  CAS  PubMed  Google Scholar 

  27. Ou DL, Chien HF, Chen CL, Lin TC, Lin LI. Role of Twist in head and neck carcinoma with lymph node metastasis. Anticancer Res. 2008;28:1355–9.

    CAS  PubMed  Google Scholar 

  28. Salerno P, Garcia-Rostan G, Piccinin S, Bencivenga TC, Di Maro G, Doglioni C, et al. TWIST1 plays a pleiotropic role in determining the anaplastic thyroid cancer phenotype. J Clin Endocrinol Metab. 2011;96:E772–81.

    Article  CAS  PubMed  Google Scholar 

  29. Singh S, Mak IW, Cowan RW, Turcotte R, Singh G, Ghert M. The role of TWIST as a regulator in giant cell tumor of bone. J Cell Biochem. 2011;112:2287–95.

    Article  CAS  PubMed  Google Scholar 

  30. Cosset E, Hamdan G, Jeanpierre S, Voeltzel T, Sagorny K, Hayette S, et al. Deregulation of TWIST-1 in the CD34+ compartment represents a novel prognostic factor in chronic myeloid leukemia. Blood. 2011;117:1673–6.

    Article  CAS  PubMed  Google Scholar 

  31. Vichalkovski A, Gresko E, Hess D, Restuccia DF, Hemmings BA. PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage. Oncogene. 2010;29:3554–65.

    Article  CAS  PubMed  Google Scholar 

  32. Cheng GZ, Chan J, Wang Q, Zhang W, Sun CD, Wang LH. Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. Cancer Res. 2007;67:1979–87.

    Article  CAS  PubMed  Google Scholar 

  33. Cheng GZ, Zhang WZ, Sun M, Wang Q, Coppola D, Mansour M, et al. Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function. J Biol Chem. 2008;283:14665–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Zhang CH, Xu GL, Jia WD, Li JS, Ma JL, Ren WH, et al. Activation of STAT3 signal pathway correlates with Twist and E-cadherin expression in hepatocellular carcinoma and their clinical significance. J Surg Res. 2012;174:120–9.

    Article  CAS  PubMed  Google Scholar 

  35. Hsu KW, Hsieh RH, Huang KH, Fen-Yau Li A, Chi CW, Wang TY, et al. Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression. Carcinogenesis. 2012;33:1459–67.

    Article  CAS  PubMed  Google Scholar 

  36. Hong J, Zhou J, Fu J, He T, Qin J, Wang L, et al. Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness. Cancer Res. 2011;71:3980–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Satoh K, Hamada S, Kimura K, Kanno A, Hirota M, Umino J, et al. Up-regulation of MSX2 enhances the malignant phenotype and is associated with twist 1 expression in human pancreatic cancer cells. Am J Pathol. 2008;172:926–39.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Lee YH, Albig AR, Regner M, Schiemann BJ, Schiemann WP. Fibulin-5 initiates epithelial-mesenchymal transition (EMT) and enhances EMT induced by TGF-beta in mammary epithelial cells via a MMP-dependent mechanism. Carcinogenesis. 2008;29:2243–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Howe LR, Watanabe O, Leonard J, Brown AM. Twist is up-regulated in response to Wnt1 and inhibits mouse mammary cell differentiation. Cancer Res. 2003;63:1906–13.

    CAS  PubMed  Google Scholar 

  40. Watanabe O, Imamura H, Shimizu T, Kinoshita J, Okabe T, Hirano A, et al. Expression of twist and wnt in human breast cancer. Anticancer Res. 2004;24:3851–6.

    CAS  PubMed  Google Scholar 

  41. Criswell TL, Arteaga CL. Modulation of NFkappaB activity and E-cadherin by the type III transforming growth factor beta receptor regulates cell growth and motility. J Biol Chem. 2007;282:32491–500.

    Article  CAS  PubMed  Google Scholar 

  42. Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, et al. Loss of MKK4 expression in ovarian cancer: a potential role for the epithelial to mesenchymal transition. Int J Cancer. 2011;128:94–104.

    Article  CAS  PubMed  Google Scholar 

  43. Kupferman ME, Jiffar T, El-Naggar A, Yilmaz T, Zhou G, Xie T, et al. TrkB induces EMT and has a key role in invasion of head and neck squamous cell carcinoma. Oncogene. 2010;29:2047–59.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Kajiro M, Hirota R, Nakajima Y, Kawanowa K, So-ma K, Ito I, et al. The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways. Nat Cell Biol. 2009;11:312–9.

    Article  CAS  PubMed  Google Scholar 

  45. Qin L, Liu Z, Chen H, Xu J. The steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis. Cancer Res. 2009;69:3819–27.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Yang MH, Hsu DS, Wang HW, Wang HJ, Lan HY, Yang WH, et al. Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nat Cell Biol. 2010;12:982–92.

    Article  PubMed  CAS  Google Scholar 

  47. Wu KJ. Direct activation of Bmi1 by Twist1: implications in cancer stemness, epithelial-mesenchymal transition, and clinical significance. Chang Gung Med J. 2011;34:229–38.

    PubMed  Google Scholar 

  48. Gort EH, van Haaften G, Verlaan I, Groot AJ, Plasterk RH, Shvarts A, et al. The TWIST1 oncogene is a direct target of hypoxia-inducible factor-2alpha. Oncogene. 2008;27:1501–10.

    Article  CAS  PubMed  Google Scholar 

  49. Yang MH, Wu KJ. TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle. 2008;7:2090–6.

    Article  CAS  PubMed  Google Scholar 

  50. Tan EJ, Thuault S, Caja L, Carletti T, Heldin CH, Moustakas A. Regulation of transcription factor Twist expression by the DNA architectural protein high mobility group A2 during epithelial-to-mesenchymal transition. J Biol Chem. 2012;287:7134–45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Zhang L, Yang M, Gan L, He T, Xiao X, Stewart MD, et al. DLX4 upregulates TWIST and enhances tumor migration, invasion and metastasis. Int J Biol Sci. 2012;8:1178–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, et al. Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol. 2002;161:1881–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Rosivatz E, Becker I, Bamba M, Schott C, Diebold J, Mayr D, et al. Neoexpression of N-cadherin in E-cadherin positive colon cancers. Int J Cancer. 2004;111:711–9.

    Article  CAS  PubMed  Google Scholar 

  54. Alexander NR, Tran NL, Rekapally H, Summers CE, Glackin C, Heimark RL. N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. Cancer Res. 2006;66:3365–9.

    Article  CAS  PubMed  Google Scholar 

  55. Zhang Z, Xie D, Li X, Wong YC, Xin D, Guan XY, et al. Significance of TWIST expression and its association with E-cadherin in bladder cancer. Hum Pathol. 2007;38:598–606.

    Article  CAS  PubMed  Google Scholar 

  56. Vesuna F, van Diest P, Chen JH, Raman V. Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer. Biochem Biophys Res Commun. 2008;367:235–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Mani SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, et al. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A. 2007;104:10069–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Shiota M, Yokomizo A, Itsumi M, Uchiumi T, Tada Y, Song Y, et al. Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer cells. BJU Int. 2011;108:E142–9.

    Article  PubMed  Google Scholar 

  59. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.

    Article  CAS  PubMed  Google Scholar 

  60. Li G, Wu Z, Peng Y, Liu X, Lu J, Wang L, et al. MicroRNA-10b induced by Epstein–Barr virus-encoded latent membrane protein-1 promotes the metastasis of human nasopharyngeal carcinoma cells. Cancer Lett. 2010;299:29–36.

    Article  CAS  PubMed  Google Scholar 

  61. Li X et al. miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011;9:824–33.

    Article  CAS  PubMed  Google Scholar 

  62. Ru P, Steele R, Newhall P, Phillips NJ, Toth K, Ray RB. MicroRNA-29b suppresses prostate cancer metastasis by regulating epithelial-mesenchymal transition signaling. Mol Cancer Ther. 2012;11:1166–73.

    Article  CAS  PubMed  Google Scholar 

  63. Li B, Han Q, Zhu Y, Yu Y, Wang J, Jiang X. Down-regulation of miR-214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist. FEBS J. 2012;279:2393–8.

    Article  CAS  PubMed  Google Scholar 

  64. Mironchik Y, Winnard Jr PT, Vesuna F, Kato Y, Wildes F, Pathak AP, et al. Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer. Cancer Res. 2005;65:10801–9.

    Article  CAS  PubMed  Google Scholar 

  65. Stoletov K, Kato H, Zardouzian E, Kelber J, Yang J, Shattil S, et al. Visualizing extravasation dynamics of metastatic tumor cells. J Cell Sci. 2010;123:2332–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Eckert MA, Yang J. Targeting invadopodia to block breast cancer metastasis. Oncotarget. 2011;2:562–8.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Sun T, Zhao N, Zhao XL, Gu Q, Zhang SW, Che N, et al. Expression and functional significance of Twist1 in hepatocellular carcinoma: its role in vasculogenic mimicry. Hepatology. 2010;51:545–56.

    Article  CAS  PubMed  Google Scholar 

  68. Pinho AV, Rooman I, Real FX. p53-dependent regulation of growth, epithelial-mesenchymal transition and stemness in normal pancreatic epithelial cells. Cell Cycle. 2011;10:1312–21.

    Article  CAS  PubMed  Google Scholar 

  69. Kwok WK, Ling MT, Yuen HF, Wong YC, Wang X. Role of p14ARF in TWIST-mediated senescence in prostate epithelial cells. Carcinogenesis. 2007;28:2467–75.

    Article  CAS  PubMed  Google Scholar 

  70. Piccinin S, Tonin E, Sessa S, Demontis S, Rossi S, Pecciarini L, et al. A “twist box” code of p53 inactivation: twist box: p53 interaction promotes p53 degradation. Cancer Cell. 2012;22:404–15.

    Article  CAS  PubMed  Google Scholar 

  71. Zhao N, Sun BC, Zhao XL, Liu ZY, Sun T, Qiu ZQ, et al. Coexpression of Bcl-2 with epithelial-mesenchymal transition regulators is a prognostic indicator in hepatocellular carcinoma. Med Oncol. 2012;29:2780–92.

    Article  CAS  PubMed  Google Scholar 

  72. Wang X, Ling MT, Guan XY, Tsao SW, Cheung HW, Lee DT, et al. Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene. 2004;23:474–82.

    Article  PubMed  CAS  Google Scholar 

  73. Chen Y, Li L, Zeng J, Wu K, Zhou J, Guo P, et al. Twist confers chemoresistance to anthracyclines in bladder cancer through upregulating P-glycoprotein. Chemotherapy. 2012;58:264–72.

    Article  CAS  PubMed  Google Scholar 

  74. Saxena M, Stephens MA, Pathak H, Rangarajan A. Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters. Cell Death Dis. 2011;2:e179.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Muñoz P, Iliou MS, Esteller M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol. 2012;6:620–36.

    Article  PubMed  CAS  Google Scholar 

  76. Vesuna F, Lisok A, Kimble B, Raman V. Twist modulates breast cancer stem cells by transcriptional regulation of CD24 expression. Neoplasia. 2009;11:1318–28.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Li J, Zhou BP. Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 2011;11:49.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  78. Srivastava RK, Tang SN, Zhu W, Meeker D, Shankar S. Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. Front Biosci (Elite Ed). 2011;3:515–28.

    Article  Google Scholar 

  79. Missaoui N, Hmissa S, Trabelsi A, Traoré C, Mokni M, Dante R, et al. Promoter hypermethylation of CDH13, DAPK1 and TWIST1 genes in precancerous and cancerous lesions of the uterine cervix. Pathol Res Pract. 2011;207:37–42.

    Article  CAS  PubMed  Google Scholar 

  80. Tsou JA, Galler JS, Siegmund KD, Laird PW, Turla S, Cozen W, et al. Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol Cancer. 2007;6:70.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  81. Dhillon VS, Aslam M, Husain SA. The contribution of genetic and epigenetic changes in granulosa cell tumors of ovarian origin. Clin Cancer Res. 2004;10:5537–45.

    Article  CAS  PubMed  Google Scholar 

  82. Schneider BG, Peng DF, Camargo MC, Piazuelo MB, Sicinschi LA, Mera R, et al. Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. Int J Cancer. 2010;127:2588–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Renard I, Joniau S, van Cleynenbreugel B, Collette C, Naômé C, Vlassenbroeck I, et al. Identification and validation of the methylated TWIST1 and NID2 genes through real-time methylation-specific polymerase chain reaction assays for the noninvasive detection of primary bladder cancer in urine samples. Eur Urol. 2010;58:96–104.

    Article  CAS  PubMed  Google Scholar 

  84. Van der Auwera I, Bovie C, Svensson C, Trinh XB, Limame R, van Dam P, et al. Quantitative methylation profiling in tumor and matched morphologically normal tissues from breast cancer patients. BMC Cancer. 2010;10:97.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  85. Mehrotra J, Vali M, McVeigh M, Kominsky SL, Fackler MJ, Lahti-Domenici J, et al. Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung. Clin Cancer Res. 2004;10:3104–9.

    Article  CAS  PubMed  Google Scholar 

  86. Gort EH, Suijkerbuijk KP, Roothaan SM, Raman V, Vooijs M, van der Wall E, et al. Methylation of the TWIST1 promoter, TWIST1 mRNA levels, and immunohistochemical expression of TWIST1 in breast cancer. Cancer Epidemiol Biomark Prev. 2008;17:3325–30.

    Article  CAS  Google Scholar 

  87. Do SI, Kim JY, Kang SY, Lee JJ, Lee JE, Nam SJ, et al. Expression of TWIST1, Snail, Slug, and NF-κB and methylation of the TWIST1 promoter in mammary phyllodes tumor. Tumor Biol. 2013;34:445–53.

    Article  CAS  Google Scholar 

  88. Zhao XL, Sun T, Che N, Sun D, Zhao N, Dong XY, et al. Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator Twist1. J Cell Mol Med. 2011;15:691–700.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Raval A, Lucas DM, Matkovic JJ, Bennett KL, Liyanarachchi S, Young DC, et al. TWIST2 demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia. J Clin Oncol. 2005;23:3877–85.

    Article  CAS  PubMed  Google Scholar 

  90. Koh HS, Lee C, Lee KS, Park EJ, Seong RH, Hong S, et al. Twist2 regulates CD7 expression and galectin-1-induced apoptosis in mature T-cells. Mol Cells. 2009;28:553–8.

    Article  CAS  PubMed  Google Scholar 

  91. Liang X, Zheng M, Jiang J, Zhu G, Yang J, Tang Y. Hypoxia-inducible factor-1 alpha, in association with TWIST2 and SNIP1, is a critical prognostic factor in patients with tongue squamous cell carcinoma. Oral Oncol. 2011;47:92–7.

    Article  CAS  PubMed  Google Scholar 

  92. Zhuo WL, Wang Y, Zhuo XL, Zhang YS, Chen ZT. Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway. Biochem Biophys Res Commun. 2008;369:1098–102.

    Article  CAS  PubMed  Google Scholar 

  93. Li QQ, Xu JD, Wang WJ, Cao XX, Chen Q, Tang F, et al. Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res. 2009;15:2657–65.

    Article  CAS  PubMed  Google Scholar 

  94. Bourguignon LY, Wong G, Earle C, Krueger K, Spevak CC. Hyaluronan-CD44 interaction promotes c-Src-mediated twist signaling, microRNA-10b expression, and RhoA/RhoC up-regulation, leading to Rho-kinase-associated cytoskeleton activation and breast tumor cell invasion. J Biol Chem. 2010;285:36721–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Xie YK, Huo SF, Zhang G, Zhang F, Lian ZP, Tang XL, et al. CDA-2 induces cell differentiation through suppressing Twist/SLUG signaling via miR-124 in glioma. J Neurooncol. 2012;110:179–86.

    Article  CAS  PubMed  Google Scholar 

  96. Haga CL, Phinney DG. MicroRNAs in the imprinted DLK1-DIO3 region repress the epithelial-to-mesenchymal transition by targeting the TWIST1 protein signaling network. J Biol Chem. 2012;287:42695–707.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Yu L, Li HZ, Lu SM, Liu WW, Li JF, Wang HB, et al. Alteration in TWIST expression: possible role in paclitaxel-induced apoptosis in human laryngeal carcinoma Hep-2 cell line. Croat Med J. 2009;50:536–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Weissenberger J, Priester M, Bernreuther C, Rakel S, Glatzel M, Seifert V, et al. Dietary curcumin attenuates glioma growth in a syngeneic mouse model by inhibition of the JAK1,2/STAT3 signaling pathway. Clin Cancer Res. 2010;16:5781–95.

    Article  CAS  PubMed  Google Scholar 

  99. Chang WW, Hu FW, Yu CC, Wang HH, Feng HP, Lan C, et al. Quercetin in elimination of tumor initiating stem-like and mesenchymal transformation property in head and neck cancer. Head Neck. 2013;35:413–9.

    Article  PubMed  Google Scholar 

  100. Dong A, Fang Y, Zhang L, Xie J, Wu X, Zhang L, et al. Caffeic acid 3,4-dihydroxy-phenethyl ester induces cancer cell senescence by suppressing twist expression. J Pharmacol Exp Ther. 2011;339:238–47.

    Article  CAS  PubMed  Google Scholar 

  101. Pai HC, Chang LH, Peng CY, Chang YL, Chen CC, Shen CC, et al. Moscatilin inhibits migration and metastasis of human breast cancer MDA-MB-231 cells through inhibition of Akt and Twist signaling pathway. J Mol Med (Berl). 2013;91:347–56.

    Article  CAS  Google Scholar 

  102. Hsu HY, Lin TY, Hwang PA, Chen RH, Tsao SM, Hsu J. Fucoidan induces changes in the epithelial-mesenchymal transition and decreases metastasis by enhancing ubiquitin-dependent TGFβ receptor degradation in breast cancer. Carcinogenesis. 2013;34:874–84.

    Article  CAS  PubMed  Google Scholar 

  103. Shimojo Y, Akimoto M, Hisanaga T, Tanaka T, Tajima Y, Honma Y, et al. Attenuation of reactive oxygen species by antioxidants suppresses hypoxia-induced epithelial-mesenchymal transition and metastasis of pancreatic cancer cells. Clin Exp Metastasis. 2013;30:143–54.

    Article  CAS  PubMed  Google Scholar 

  104. Guo Y, Xie J, Rubin E, Tang YX, Lin F, Zi X, et al. Frzb, a secreted Wnt antagonist, decreases growth and invasiveness of fibrosarcoma cells associated with inhibition of Met signaling. Cancer Res. 2008;68:3350–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Chung MT, Lai HC, Sytwu HK, Yan MD, Shih YL, Chang CC, et al. SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway. Gynecol Oncol. 2009;112:646–53.

    Article  CAS  PubMed  Google Scholar 

  106. Yee DS et al. The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition. Mol Cancer. 2010;9:162.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  107. Na YR, Seok SH, Kim DJ, Han JH, Kim TH, Jung H, et al. Bone morphogenetic protein 7 induces mesenchymal-to-epithelial transition in melanoma cells, leading to inhibition of metastasis. Cancer Sci. 2009;100:2218–25.

    Article  CAS  PubMed  Google Scholar 

  108. Merikallio H, Kaarteenaho R, Pääkkö P, Lehtonen S, Hirvikoski P, Mäkitaro R, et al. Zeb1 and twist are more commonly expressed in metastatic than primary lung tumours and show inverse associations with claudins. J Clin Pathol. 2011;64:136–40.

    Article  PubMed  Google Scholar 

  109. Lee KW, Lee NK, Kim JH, Kang MS, Yoo HY, Kim HH, et al. Twist1 causes the transcriptional repression of claudin-4 with prognostic significance in esophageal cancer. Biochem Biophys Res Commun. 2012;423:454–60.

    Article  CAS  PubMed  Google Scholar 

  110. Stasinopoulos IA, Mironchik Y, Raman A, Wildes F, Winnard Jr P, Raman V. HOXA5-twist interaction alters p53 homeostasis in breast cancer cells. J Biol Chem. 2005;280:2294–9.

    Article  CAS  PubMed  Google Scholar 

  111. Fu J, Qin L, He T, Qin J, Hong J, Wong J, et al. The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis. Cell Res. 2011;21:275–89.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  112. Demontis S, Rigo C, Piccinin S, Mizzau M, Sonego M, Fabris M, et al. Twist is substrate for caspase cleavage and proteasome-mediated degradation. Cell Death Differ. 2006;13:335–45.

    Article  CAS  PubMed  Google Scholar 

  113. Zhong J, Ogura K, Wang Z, Inuzuka H. Degradation of the transcription factor Twist, an oncoprotein that promotes cancer metastasis. Discov Med. 2013;15:7–15.

    PubMed  Google Scholar 

  114. Fu J, Zhang L, He T, Xiao X, Liu X, Wang L, et al. TWIST represses estrogen receptor-α expression epigenetically by recruiting the NuRD protein complex in breast cancer cells. Endocr Rev. 2012;33:OR36–3.

    Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81172049, 30371493) and the Innovation Team of Education Bureau of Sichuan Province (13TD0032) to J. Fu. We apologize sincerely to colleagues whose contributions are not cited due to space limitations.

Conflicts of interest

The authors have no conflict of interest regarding this article.

Author information

Authors and Affiliations

  1. Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Luzhou Medical College, 3-319 Zhongshan Road, Luzhou, Sichuan, 646000, China

    Md. Asaduzzaman Khan & Junjiang Fu

  2. Department of Biochemistry, School of Life Sciences, Central South University, Changsha, Hunan, 410013, China

    Md. Asaduzzaman Khan & Han-chun Chen

  3. Department of Biochemistry/Molecular Biology, Philadelphia College of Osteopathic Medicine Philadelphia, Philadelphia, PA, 19131, USA

    Dianzheng Zhang

Authors
  1. Md. Asaduzzaman Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Han-chun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dianzheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junjiang Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Junjiang Fu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khan, M.A., Chen, Hc., Zhang, D. et al. Twist: a molecular target in cancer therapeutics. Tumor Biol. 34, 2497–2506 (2013). https://doi.org/10.1007/s13277-013-1002-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-1002-x

Keywords

Search

Navigation