Twisti gene

The TWISTI1 gene, which is located on chromosome 7p21.1, encodes a protein which, as a transcription factor, controls the activities of various genes. TWISTI protein is a member of a large group of transcription factors known as basic helix-loop-helix factors, also known as bHLH, which are responsible for the development of many organs during embryogenesis, including bone development.

The protein is also known as an oncogene, as it is upregulated in various tumours, such as neuroblastoma. TWISTI is not present in normal lymphocytes, but it can be massively detected in Sézary cells (mutations in the TWISTI gene are detected in Sézary syndrome) Twist induces the expression of DNM3 and DNM3os. DNM3 contains miR-199a2/214, which in Sézary syndrome represents the majority of aberrantly expressed microRNAs. Twist could play a decisive role in the pathogenesis of Sézary syndrome via this upregulation.

Twist is up-regulated by numerous activators such as the activator of transcription 3(STAT3) and the mitogen-activated protein kinase(RAS). The activated TWIST gene upregulates N-cadherin and suppresses E-cadherin, which are key functions of EMT (= "epithelial-mesenchymal transition", a process in which epithelial cells lose their cell polarity and cell-cell adhesion and regain migratory and invasive properties). Twist also plays an important role in various physiological processes involved in metastasis, including angiogenesis and extravasation. Twist prevents apoptosis in tumour cells and also appears to be involved in the development of tumours' resistance to chemotherapeutic agents.

1. Howard TD et al (1997) "Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome". Nature Genetics 15: 36-41.
2. Martin TA et al (2005) "Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer". Annals of Surgical Oncology 12: 488-496.
3. Nicolay JP et al (2016) The Sézary syndrome: from unresolved questions to new therapeutic approaches. SDDG 14: 256-265.