Basic helix-loop-helix (bHLH) transcription factors have been implicated in cell lineage determination and differentiation. The protein encoded by this gene is abHLH transcription factor and shares similarity with another bHLH transcription factor, Dermo1 (a.k.a.TWIST2). The strongest expression of this mRNA is in placental tissue; in adults, mesodermally derived tissues express this mRNA preferentially.[7]
Twist plays an essential role in cancer metastasis. Over-expression of Twist ormethylation of itspromoter is common inmetastatic carcinomas. Hence targeting Twist has a great promise as a cancer therapeutic.[14] In cooperation withN-Myc, Twist-1 acts as anoncogene in several cancers includingneuroblastoma.[11][15]
Twist is activated by a variety ofsignal transduction pathways, includingAkt, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase,Ras, andWnt signaling. Activated Twist upregulatesN-cadherin and downregulatesE-cadherin, which are the hallmarks ofEMT. 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 maintenance of cancer stem cells and the development of chemotherapy resistance.[14][16] Twist1 is extensively studied for its role in head- and neck cancers.[17] Here and in epithelial ovarian cancer, Twist1 has been shown to be involved in evading apoptosis, making the tumour cells resistant against platinum-based chemotherapeutic drugs like cisplatin.[16][18] Moreover, Twist1 has been shown to be expressed under conditions of hypoxia, corresponding to the observation that hypoxic cells respond less to chemotherapeutic drugs.[17]
Another process in which Twist 1 is involved is tumour metastasis. The underlying mechanism is not completely understood, but it has been implicated in the upregulation ofmatrix metalloproteinases[19] and inhibition ofTIMP.[20]
Recently, targeting Twist has gained interest as a target for cancer therapeutics. The inactivation of Twist bysmall interfering RNA orchemotherapeutic approach has been demonstratedin vitro. Moreover, several inhibitors which are antagonistic to the upstream or downstream molecules of Twist signaling pathways have also been identified.[14]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Bourgeois P, Stoetzel C, Bolcato-Bellemin AL, Mattei MG, Perrin-Schmitt F (Dec 1996). "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".Mammalian Genome.7 (12):915–7.doi:10.1007/s003359900269.PMID8995765.S2CID42710079.
^Howard TD, Paznekas WA, Green ED, Chiang LC, Ma N, Ortiz de Luna RI, Garcia Delgado C, Gonzalez-Ramos M, Kline AD, Jabs EW (Jan 1997). "Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome".Nature Genetics.15 (1):36–41.doi:10.1038/ng0197-36.PMID8988166.S2CID35360537.
^abMartin TA, Goyal A, Watkins G, Jiang WG (Jun 2005). "Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer".Annals of Surgical Oncology.12 (6):488–96.doi:10.1245/ASO.2005.04.010.PMID15864483.S2CID19102926.
^van Doorn R, Dijkman R, Vermeer MH, Out-Luiting JJ, van der Raaij-Helmer EM, Willemze R, Tensen CP (Aug 2004). "Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in Sézary syndrome identified by gene expression analysis".Cancer Research.64 (16):5578–86.doi:10.1158/0008-5472.CAN-04-1253.PMID15313894.S2CID6506412.
^abWu KJ, Yang MH (Dec 2011). "Epithelial-mesenchymal transition and cancer stemness: the Twist1-Bmi1 connection".Bioscience Reports.31 (6):449–55.doi:10.1042/BSR20100114.PMID21919891.S2CID16648243.
^Zhuo WL, Wang Y, Zhuo XL, Zhang YS, Chen ZT (May 2008). "Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway".Biochemical and Biophysical Research Communications.369 (4):1098–102.doi:10.1016/j.bbrc.2008.02.143.PMID18331824.
Seto ML, Lee SJ, Sze RW, Cunningham ML (Dec 2001). "Another TWIST on Baller-Gerold syndrome".American Journal of Medical Genetics.104 (4):323–30.doi:10.1002/ajmg.10065.PMID11754069.
Bianchi DW, Cirillo-Silengo M, Luzzatti L, Greenstein RM (Jun 1981). "Interstitial deletion of the short arm of chromosome 7 without craniosynostosis".Clinical Genetics.19 (6):456–61.doi:10.1111/j.1399-0004.1981.tb02064.x.PMID7296937.S2CID25464482.
Maw M, Kar B, Biswas J, Biswas P, Nancarrow D, Bridges R, Kumaramanickavel G, Denton M, Badrinath SS (Dec 1996). "Linkage of blepharophimosis syndrome in a large Indian pedigree to chromosome 7p".Human Molecular Genetics.5 (12):2049–54.doi:10.1093/hmg/5.12.2049.PMID8968762.
el Ghouzzi V, Le Merrer M, Perrin-Schmitt F, Lajeunie E, Benit P, Renier D, Bourgeois P, Bolcato-Bellemin AL, Munnich A, Bonaventure J (Jan 1997). "Mutations of the TWIST gene in the Saethre-Chotzen syndrome".Nature Genetics.15 (1):42–6.doi:10.1038/ng0197-42.PMID8988167.S2CID22140671.
Wang SM, Coljee VW, Pignolo RJ, Rotenberg MO, Cristofalo VJ, Sierra F (Mar 1997). "Cloning of the human twist gene: its expression is retained in adult mesodermally-derived tissues".Gene.187 (1):83–92.doi:10.1016/S0378-1119(96)00727-5.PMID9073070.
Gripp KW, Stolle CA, Celle L, McDonald-McGinn DM, Whitaker LA, Zackai EH (Jan 1999). "TWIST gene mutation in a patient with radial aplasia and craniosynostosis: further evidence for heterogeneity of Baller-Gerold syndrome".American Journal of Medical Genetics.82 (2):170–6.doi:10.1002/(SICI)1096-8628(19990115)82:2<170::AID-AJMG14>3.0.CO;2-X.PMID9934984.
Lee MS, Lowe G, Flanagan S, Kuchler K, Glackin CA (Nov 2000). "Human Dermo-1 has attributes similar to twist in early bone development".Bone.27 (5):591–602.doi:10.1016/S8756-3282(00)00380-X.PMID11062344.
