Review

Tumor Biology

, Volume 34, Issue 5, pp 2497-2506

First online:

Twist: a molecular target in cancer therapeutics

  • Md. Asaduzzaman KhanAffiliated withKey Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Luzhou Medical CollegeDepartment of Biochemistry, School of Life Sciences, Central South University
  • , Han-chun ChenAffiliated withDepartment of Biochemistry, School of Life Sciences, Central South University
  • , Dianzheng ZhangAffiliated withDepartment of Biochemistry/Molecular Biology, Philadelphia College of Osteopathic Medicine Philadelphia
  • , Junjiang FuAffiliated withKey Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Luzhou Medical College Email author 

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Abstract

Twist, the basic helix-loop-helix transcription factor, is involved in the process of epithelial to mesenchymal transitions (EMTs), which play an essential role in cancer metastasis. Overexpression of Twist or its promoter methylation is a common scenario in metastatic carcinomas. Twist is activated by a variety of signal transduction pathways, including Akt, signal transducer and activator of transcription 3, 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 stemness of cancer cells and the generation of drug resistance. Recently, targeting Twist has gained significant interests in cancer therapeutics. The inactivation of Twist by small RNA technology or chemotherapeutic approach has been proved successful. Moreover, several inhibitors which are antagonistic to the upstream or downstream molecules of Twist signaling pathways have also been identified. Development of potential treatment strategies by targeting Twist has a great promise in cancer therapeutics.

Keywords

Twist Metastasis Epithelial to mesenchymal transition Epigenetic changes Cancer stem cells Cancer therapy