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, Twist1 has been shown to be involved in evading apoptosis, making the tumour cells resistant against 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.
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 
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