Twist-related protein 1 (Twist1) (TWIST1)

Twist-related protein 1 (Twist1) is a basic helix-loop-helix (bHLH) transcription factor that serves as a master regulator of cell plasticity, particularly through the induction of the Endothelial-to-Mesenchymal Transition (EndMT) [UniProt Q15672]. In this process, Twist1 represses the transcription of Vascular Endothelial Cadherin (VE-cadherin/CDH5), a key protein responsible for maintaining endothelial cell-cell junctions and vascular integrity [PMID: 25344711]. The loss of VE-cadherin mediated by Twist1 leads to increased vascular permeability and allows endothelial cells to adopt a migratory, mesenchymal phenotype [PMID: 26073077]. This regulatory axis is a critical driver in various pathologies, including cancer metastasis, where it facilitates tumor cell intravasation, and organ fibrosis, where it contributes to the accumulation of myofibroblasts [PMID: 24213477]. Consequently, Twist1 is considered a high-value therapeutic target for preventing metastatic progression and fibrotic tissue remodeling. Current pharmacological efforts focus on small molecule inhibitors like harmine that promote Twist1 degradation or disrupt its interaction with transcriptional co-activators [PMID: 22431510]. Achieving high specificity for this transcription factor remains a significant challenge in drug development due to its structural properties and role in normal development. Targeting the Twist1-VE-cadherin axis offers a potential strategy to stabilize the vasculature and inhibit disease progression.

Other names

TWISTBHLHA38Class A basic helix-loop-helix protein 38Saethre-Chotzen syndrome proteinSCSACS3CRS1

Inhibition of Twist1-mediated transcriptional repression of CDH5 (VE-cadherin) by targeting the Twist1 protein for degradation or blocking its DNA-binding domain [PMID: 22431510].