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Gene Review

TWIST1  -  twist family bHLH transcription factor 1

Homo sapiens

Synonyms: ACS3, BHLHA38, BPES2, BPES3, CRS, ...
Twist1 and Twist2 were first associated to cancer based on their ability to promote bypass of p53 response. In fact, both genes were isolated through a genetic screen for cDNAs capable of overriding oncogene-induced apoptosis and demonstrated to be overexpressed in human tumors [1].

Disease relevance of TWIST1


Psychiatry related information on TWIST1

  • Static and dynamic contrast sensitivity (SCS and DCS), semantic object identification, and verbal recall functions were evaluated in 20 Alzheimer's disease (AD) patients and in 20 control subjects [6].
  • In an attempt to address and in part replicate the above findings among panic disorder patients, we adopted the SCS of Margraf et al [7].
  • DISCUSSION: The discussion highlights the prominent role that SCS scores, self-efficacy and especially perceived quitting difficulty play in the smoking cessation process [8].
  • The SCS/ARS/CES pesticide properties database for environmental decision-making [9].
  • Depressive symptoms were significantly correlated with the SCS (r = 0.52, p = 0.001), specifically perceived group membership (r = 0.56, p < 0.001) [10].

High impact information on TWIST1

  • hsp90: Twist and Fold [11].
  • A recent report in Cell (Yang et al., 2004) adds Twist to this list and links EMT to the ability of breast cancer cells to enter the circulation and seed metastases [12].
  • Adenovirus E1A protein mimics the effects of Twist by inhibiting the HAT activities of p300 and PCAF [13].
  • Furthermore, inhibition of NF-kappaB activity in limb mesenchyme leads to a reduction in expression of Sonic hedgehog and Twist but derepresses expression of the bone morphogenetic protein-4 gene [14].
  • Repression of E-cadherin by transcriptional regulators such as Snail or Twist emerges as one critical step driving EMT, and this stage is currently being molecularly linked with many of the new players [15].

Chemical compound and disease context of TWIST1

  • These data raise the possibility that integrin-mediated adhesion to interstitial matrix proteins during metastasis differentially regulates the nuclear/cytoplasmic translocation and DNA binding of Twist1, activating N-cadherin transcription [16].

Biological context of TWIST1

  • The biologic activity of TWIST1 has been implicated in the inhibition of differentiation of multiple cell lineages [17].
  • Prior to our study, there were no published TWIST1 mutations in the anti-osteogenic C-terminus, recently coined the TWIST Box, which binds and inhibits RUNX2 transactivation [3].
  • In osteoblast-like cell culture, BMP-2 enhanced osteoblast-related gene expression, while Twist expression was slightly decreased [18].
  • Thus, the loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis [19].
  • Expression of Twist but not a frame shift mutation of Twist activates the wild-type human GLI1 regulatory sequences but not with inactivating mutations of the E-boxes [4].
  • The transcriptional activating function of Twist was mapped to conserved aminoacid residues in the C-terminal TWIST box [20].

Anatomical context of TWIST1


Associations of TWIST1 with chemical compounds

  • Moreover, the tyrosine kinase receptor EphA4 and the potentially oncogenic transcription factor Twist were highly and selectively expressed in T cells of patients with Sz [25].
  • Morphometric analysis showed that the ionophore caused extensive degranulation in both types of platelets (decrease of the granule volume), which occurred in the presence of contraction of thrombasthenic PRP (decrease of the SCS plus granule volume) but in its absence in EDTA-treated platelets [26].
  • The increased nuclear accumulation of Twist1 following cell attachment was suppressed by treatment with an inhibitor of Rho kinase or a beta(1) integrin neutralizing antibody [16].
  • Identification and purification of a human Sertoli cell-secreted protein (hSCSP-80) stimulating Leydig cell steroid biosynthesis [27].
  • RmlC, a C3' and C5' Carbohydrate Epimerase, Appears to Operate via an Intermediate with an Unusual Twist Boat Conformation [28].
  • Twist-1 is an evolutionarily conserved target of NF-kappaB, blocks PCD induced by chemotherapeutic drugs and TNF-alpha in NF-kappaB-deficient cells, and is essential to counter this PCD in cancer cells [29].

Regulatory relationships of TWIST1

  • Interestingly, unlike in osteoblast-like cells, Twist expression was upregulated by BMP-2 in PDL cells [18].
  • This provides genetic and biochemical evidence for a role of Fgfr2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in the SCS [30].
  • These results indicate that, during osteoblast development, Dermo-1 may inhibit osteoblast maturation and maintain cells in a preosteoblast phenotype by utilizing mechanisms similar but not identical to those utilized by Twist [31].
  • BACKGROUND: Slug, Snail, and Twist are transcription factors that regulate the expression of tumor suppressors such as E-cadherin [32].
  • We reported Twist expression was regulated by Wnt/beta-catenin signaling and that both Wnt-1 and Twist could contribute to mammary tumorigenesis [33].

Other interactions of TWIST1

  • We investigated the localization of Twist in PDL and compared the expression of Twist and osteoblast-related genes in PDL cells with those in osteoblast-like cells in the presence or absence of recombinant human bone morphogenetic protein (BMP)-2 [18].
  • Seathre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome, associated with loss-of-function mutations in the basic helix-loop-helix transcription factor, TWIST1 [17].
  • Searching for potential protein interacting partners we found that HOXA5 binds to an anti-apoptotic protein, Twist [19].
  • Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to gamma-radiation and decreased regulation of downstream target genes [19].
  • By using logic regression, we determined that the best panel of hypermethylated genes included DAPK1, RARB, or TWIST1 [34].

Analytical, diagnostic and therapeutic context of TWIST1

  • Methylated alleles of Cyclin D2, RAR-beta, and Twist genes were frequently detected in fluid from mammary ducts containing endoscopically visualised carcinomas (17 cases of 20), and ductal carcinoma in situ (two of seven), but rarely in ductal lavage fluid from healthy ducts (five of 45) [35].
  • Double label immunofluorescent staining of frozen sections of ovary with the SCS antiserum and an antibody to the cortical granule protein hyalin indicated a dramatic morphogenesis of the SCS-containing ER (SCS-ER) coincident with oocyte maturation [36].
  • Immunoelectron microscopy also revealed that SCS is not present in golgi complexes of oocytes [36].
  • Electrical stimulation of the spinal cord (SCS) to reduce spasticity was evaluated in seven patients who, along with their physicians, perceived significant and prompt benefit from stimulation [37].
  • Using electron microscopy we found that 7E3-occupied GPIIb-IIIa complexes are internalized into the surface connected system (SCS) and the alpha-granules of washed platelets which was associated with a reduced degranulation of the alpha-granula membrane protein P-selectin [38].



  1. Twist is a potential oncogene that inhibits apoptosis. Maestro, R., Dei Tos, A.P., Hamamori, Y., Krasnokutsky, S., Sartorelli, V., Kedes, L., Doglioni, C., Beach, D.H., Hannon, G.J. Genes. Dev. (1999) [Pubmed]
  2. Large-scale molecular comparison of human schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues. Miller, S.J., Rangwala, F., Williams, J., Ackerman, P., Kong, S., Jegga, A.G., Kaiser, S., Aronow, B.J., Frahm, S., Kluwe, L., Mautner, V., Upadhyaya, M., Muir, D., Wallace, M., Hagen, J., Quelle, D.E., Watson, M.A., Perry, A., Gutmann, D.H., Ratner, N. Cancer Res. (2006) [Pubmed]
  3. Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations. Seto, M.L., Hing, A.V., Chang, J., Hu, M., Kapp-Simon, K.A., Patel, P.K., Burton, B.K., Kane, A.A., Smyth, M.D., Hopper, R., Ellenbogen, R.G., Stevenson, K., Speltz, M.L., Cunningham, M.L. Am. J. Med. Genet. A (2007) [Pubmed]
  4. Cooperative E-box regulation of human GLI1 by TWIST and USF. Villavicencio, E.H., Yoon, J.W., Frank, D.J., Füchtbauer, E.M., Walterhouse, D.O., Iannaccone, P.M. Genesis (2002) [Pubmed]
  5. Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells. Valsesia-Wittmann, S., Magdeleine, M., Dupasquier, S., Garin, E., Jallas, A.C., Combaret, V., Krause, A., Leissner, P., Puisieux, A. Cancer Cell (2004) [Pubmed]
  6. Early visual impairment is independent of the visuocognitive and memory disturbances in Alzheimer's disease. Kéri, S., Antal, A., Kálmán, J., Janka, Z., Benedek, G. Vision Res. (1999) [Pubmed]
  7. Do panic disorder patients indiscriminately endorse somatic complaints? Goetz, R.R., Gorman, J.M., Dillon, D.J., Papp, L.A., Hollander, E., Fyer, A.J., Liebowitz, M.R., Klein, D.F. Psychiatry research. (1989) [Pubmed]
  8. Learned resourcefulness and smoking cessation revisited. Kennett, D.J., Morris, E., Bangs, A.M. Patient education and counseling. (2006) [Pubmed]
  9. The SCS/ARS/CES pesticide properties database for environmental decision-making. Wauchope, R.D., Buttler, T.M., Hornsby, A.G., Augustijn-Beckers, P.W., Burt, J.P. Reviews of environmental contamination and toxicology. (1992) [Pubmed]
  10. Social comparison processes and depressive symptoms in children and adolescents with Asperger syndrome. Hedley, D., Young, R. Autism : the international journal of research and practice. (2006) [Pubmed]
  11. hsp90: Twist and Fold. Richter, K., Buchner, J. Cell (2006) [Pubmed]
  12. Epithelial-mesenchymal transitions: twist in development and metastasis. Kang, Y., Massagué, J. Cell (2004) [Pubmed]
  13. Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A. Hamamori, Y., Sartorelli, V., Ogryzko, V., Puri, P.L., Wu, H.Y., Wang, J.Y., Nakatani, Y., Kedes, L. Cell (1999) [Pubmed]
  14. Inhibition of NF-kappaB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis. Bushdid, P.B., Brantley, D.M., Yull, F.E., Blaeuer, G.L., Hoffman, L.H., Niswander, L., Kerr, L.D. Nature (1998) [Pubmed]
  15. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Huber, M.A., Kraut, N., Beug, H. Curr. Opin. Cell Biol. (2005) [Pubmed]
  16. N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. Alexander, N.R., Tran, N.L., Rekapally, H., Summers, C.E., Glackin, C., Heimark, R.L. Cancer Res. (2006) [Pubmed]
  17. In vitro differentiation profile of osteoblasts derived from patients with Saethre-Chotzen syndrome. Ratisoontorn, C., Seto, M.L., Broughton, K.M., Cunningham, M.L. Bone (2005) [Pubmed]
  18. Twist negatively regulates osteoblastic differentiation in human periodontal ligament cells. Komaki, M., Karakida, T., Abe, M., Oida, S., Mimori, K., Iwasaki, K., Noguchi, K., Oda, S., Ishikawa, I. J. Cell. Biochem. (2007) [Pubmed]
  19. HOXA5-twist interaction alters p53 homeostasis in breast cancer cells. Stasinopoulos, I.A., Mironchik, Y., Raman, A., Wildes, F., Winnard, P., Raman, V. J. Biol. Chem. (2005) [Pubmed]
  20. Mechanism of transcriptional activation by the proto-oncogene Twist1. Laursen, K.B., Mielke, E., Iannaccone, P., Füchtbauer, E.M. J. Biol. Chem. (2007) [Pubmed]
  21. TWIST inactivation reduces CBFA1/RUNX2 expression and DNA binding to the osteocalcin promoter in osteoblasts. Yousfi, M., Lasmoles, F., Marie, P.J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  22. Twist1 dimer selection regulates cranial suture patterning and fusion. Connerney, J., Andreeva, V., Leshem, Y., Muentener, C., Mercado, M.A., Spicer, D.B. Dev. Dyn. (2006) [Pubmed]
  23. Unique CCT repeats mediate transcription of the TWIST1 gene in mesenchymal cell lines. Ohkuma, M., Funato, N., Higashihori, N., Murakami, M., Ohyama, K., Nakamura, M. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  24. Characterization of a dominant negative C. elegans Twist mutant protein with implications for human Saethre-Chotzen syndrome. Corsi, A.K., Brodigan, T.M., Jorgensen, E.M., Krause, M. Development (2002) [Pubmed]
  25. Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in Sézary syndrome identified by gene expression analysis. van Doorn, R., Dijkman, R., Vermeer, M.H., Out-Luiting, J.J., van der Raaij-Helmer, E.M., Willemze, R., Tensen, C.P. Cancer Res. (2004) [Pubmed]
  26. Human platelet activation in the absence of aggregation: a calcium-dependent phenomenon independent of thromboxane formation. Levy-Toledano, S., Maclouf, J., Bryon, P., Savariau, E., Hardisty, R.M., Caen, J.P. Blood (1982) [Pubmed]
  27. Identification and purification of a human Sertoli cell-secreted protein (hSCSP-80) stimulating Leydig cell steroid biosynthesis. Papadopoulos, V. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  28. RmlC, a C3' and C5' Carbohydrate Epimerase, Appears to Operate via an Intermediate with an Unusual Twist Boat Conformation. Dong, C., Major, L.L., Srikannathasan, V., Errey, J.C., Giraud, M.F., Lam, J.S., Graninger, M., Messner, P., McNeil, M.R., Field, R.A., Whitfield, C., Naismith, J.H. J. Mol. Biol. (2007) [Pubmed]
  29. Upregulation of Twist-1 by NF-kappaB blocks cytotoxicity induced by chemotherapeutic drugs. Pham, C.G., Bubici, C., Zazzeroni, F., Knabb, J.R., Papa, S., Kuntzen, C., Franzoso, G. Mol. Cell. Biol. (2007) [Pubmed]
  30. A role for fibroblast growth factor receptor-2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in the Saethre-Chotzen syndrome. Guenou, H., Kaabeche, K., Mée, S.L., Marie, P.J. Hum. Mol. Genet. (2005) [Pubmed]
  31. Human Dermo-1 has attributes similar to twist in early bone development. Lee, M.S., Lowe, G., Flanagan, S., Kuchler, K., Glackin, C.A. Bone (2000) [Pubmed]
  32. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Martin, T.A., Goyal, A., Watkins, G., Jiang, W.G. Ann. Surg. Oncol. (2005) [Pubmed]
  33. Expression of twist and wnt in human breast cancer. Watanabe, O., Imamura, H., Shimizu, T., Kinoshita, J., Okabe, T., Hirano, A., Yoshimatsu, K., Konno, S., Aiba, M., Ogawa, K. Anticancer Res. (2004) [Pubmed]
  34. Detection of hypermethylated genes in women with and without cervical neoplasia. Feng, Q., Balasubramanian, A., Hawes, S.E., Toure, P., Sow, P.S., Dem, A., Dembele, B., Critchlow, C.W., Xi, L., Lu, H., McIntosh, M.W., Young, A.M., Kiviat, N.B. J. Natl. Cancer Inst. (2005) [Pubmed]
  35. Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Evron, E., Dooley, W.C., Umbricht, C.B., Rosenthal, D., Sacchi, N., Gabrielson, E., Soito, A.B., Hung, D.T., Ljung, B., Davidson, N.E., Sukumar, S. Lancet (2001) [Pubmed]
  36. Differentiation of a calsequestrin-containing endoplasmic reticulum during sea urchin oogenesis. Henson, J.H., Beaulieu, S.M., Kaminer, B., Begg, D.A. Dev. Biol. (1990) [Pubmed]
  37. Evaluation of cervical stimulation for chronic treatment of spasticity. Gottlieb, G.L., Myklebust, B.M., Stefoski, D., Groth, K., Kroin, J., Penn, R.D. Neurology (1985) [Pubmed]
  38. Incomplete inhibition of platelet aggregation and glycoprotein IIb-IIIa receptor blockade by abciximab: importance of internal pool of glycoprotein IIb-IIIa receptors. Gawaz, M., Ruf, A., Pogatsa-Murray, G., Dickfeld, T., Rüdiger, S., Taubitz, W., Fischer, J., Müller, I., Meier, D., Patscheke, H., Schömig, A. Thromb. Haemost. (2000) [Pubmed]
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