Basic helix-loop-helix (bHLH) transcription factors have been implicated in cell lineage determination and differentiation. The protein encoded by this gene is a bHLH 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.
Twist is activated by a variety of signal transduction pathways, including Akt, signal transducer and activator of transcription 3 (STAT3), 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 maintenance of cancer stem cells and the development of chemotherapy resistance. Twist1 is extensively studied for its role in head- and neck cancers. 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. Moreover, Twist1 has been shown to be expressed under conditions of hypoxia, corresponding to the observation that hypoxic cells respond less to chemotherapeutic drugs.
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 of matrix metalloproteinases and inhibition of TIMP.
Recently, targeting Twist has gained interest as a target for cancer therapeutics. The inactivation of Twist by small interfering RNA or chemotherapeutic approach has been demonstrated in vitro. Moreover, several inhibitors which are antagonistic to the upstream or downstream molecules of Twist signaling pathways have also been identified. For example, thymoquinone, a natural product downregulates TWIST1 transcription factor to reduce epithelial to mesenchymal transition, and thus inhibits cancer metastasis in cancer cell lines and xenograft model of breast cancer in mouse 
^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.
^Kress W, Schropp C, Lieb G, Petersen B, Büsse-Ratzka M, Kunz J, Reinhart E, Schäfer WD, Sold J, Hoppe F, Pahnke J, Trusen A, Sörensen N, Krauss J, Collmann H (Jan 2006). "Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome". European Journal of Human Genetics. 14 (1): 39–48. doi:10.1038/sj.ejhg.5201507. PMID16251895.
^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.
^ 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.
^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.
^ 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.
^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.
^Zhao XL, Sun T, Che N, Sun D, Zhao N, Dong XY, Gu Q, Yao Z, Sun BC (Mar 2011). "Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator Twist1". Journal of Cellular and Molecular Medicine. 15 (3): 691–700. doi:10.1111/j.1582-4934.2010.01052.x. PMID20219012.
^Okamura H, Yoshida K, Haneji T (Jul 2009). "Negative regulation of TIMP1 is mediated by transcription factor TWIST1". International Journal of Oncology. 35 (1): 181–6. doi:10.3892/ijo_00000327. PMID19513566.
^ abHamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L (Feb 1999). "Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A". Cell. 96 (3): 405–13. doi:10.1016/S0092-8674(00)80553-X. PMID10025406.
^El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, Bonaventure J (Mar 2000). "Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location". Human Molecular Genetics. 9 (5): 813–9. doi:10.1093/hmg/9.5.813. PMID10749989.
Rose CS, King AA, Summers D, Palmer R, Yang S, Wilkie AO, Reardon W, Malcolm S, Winter RM (Aug 1994). "Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2". Human Molecular Genetics. 3 (8): 1405–8. doi:10.1093/hmg/3.8.1405. PMID7987323.
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.
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.
Krebs I, Weis I, Hudler M, Rommens JM, Roth H, Scherer SW, Tsui LC, Füchtbauer EM, Grzeschik KH, Tsuji K, Kunz J (Jul 1997). "Translocation breakpoint maps 5 kb 3' from TWIST in a patient affected with Saethre-Chotzen syndrome". Human Molecular Genetics. 6 (7): 1079–86. doi:10.1093/hmg/6.7.1079. PMID9215678.
Rose CS, Patel P, Reardon W, Malcolm S, Winter RM (Aug 1997). "The TWIST gene, although not disrupted in Saethre-Chotzen patients with apparently balanced translocations of 7p21, is mutated in familial and sporadic cases". Human Molecular Genetics. 6 (8): 1369–73. doi:10.1093/hmg/6.8.1369. PMID9259286.
Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L (Feb 1999). "Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A". Cell. 96 (3): 405–13. doi:10.1016/S0092-8674(00)80553-X. PMID10025406.
Elanko N, Sibbring JS, Metcalfe KA, Clayton-Smith J, Donnai D, Temple IK, Wall SA, Wilkie AO (Dec 2001). "A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals". Human Mutation. 18 (6): 535–41. doi:10.1002/humu.1230. PMID11748846.