A twist tale of cancer metastasis and tumor angiogenesis

Histol Histopathol. 2015 Nov;30(11):1283-94. doi: 10.14670/HH-11-638. Epub 2015 Jun 18.


Twist1 is an evolutionally conserved transcription factor. Originally identified in Drosophila as a key regulator for mesoderm development, it was later implicated in many human diseases, including Saethre-Chotzen syndrome and cancer. Twist1's involvement in cancer has been well recognized. Driven by hypoxia-induced factor-1 (HIF-1), Twist1 has been considered as a proto-oncogene and its overexpression has been observed in a wide variety of human cancers. High expression level of Twist1 is closely related to tumor aggressiveness and metastatic potential. In cancer cells, Twist1 has been shown to function as a key regulator of epithelial-mesenchymal transition (EMT), a critical process for metastasis initiation. Twist1 has also been implicated in maintaining cancer stemness for self-renewal and chemoresistance. This review first summarizes the roles of Twist1 in embryo development and Saethre-Chotzen syndrome followed by a discussion of Twist1's critical functions in cancer. In particular, the review focuses on the recent discovery of Twist1's capability to promote endothelial transdifferentiation of cancer cells beyond EMT.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acrocephalosyndactylia / genetics
  • Acrocephalosyndactylia / metabolism
  • Animals
  • Cell Movement*
  • Cell Transdifferentiation
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Humans
  • Morphogenesis
  • Neoplasm Metastasis
  • Neoplasms / blood supply
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neovascularization, Pathologic*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phenotype
  • Proto-Oncogene Mas
  • Signal Transduction
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*


  • MAS1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Mas
  • TWIST1 protein, human
  • Twist-Related Protein 1