AKT-ions with a TWIST between EMT and MET

Huifang Tang _, Daniela Massi, Brian A. Hemmings, Mario Mandalà, Zhengqiang Hu, Andreas Wicki and Gongda Xue

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Oncotarget. 2016; 7:62767-62777. https://doi.org/10.18632/oncotarget.11232

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Huifang Tang1, Daniela Massi2, Brian A. Hemmings3, Mario Mandalà4, Zhengqiang Hu1, Andreas Wicki5 and Gongda Xue5

1 Department of Pharmacology, Zhejiang University, School of Basic Medical Sciences, Hangzhou, China

2 Department of Surgery and Translational Medicine, University of Florence, Florence, Italy

3 Department of Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

4 Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy

5 Department of Biomedicine, University Hospital Basel, Basel, Switzerland

Correspondence to:

Huifang Tang, email:

Gongda Xue, email:

Keywords: epithelial-mesenchymal transition, Twist, Akt, plasticity, phosphorylation

Received: May 22, 2016 Accepted: July 28, 2016 Published: August 11, 2016


The transcription factor Twist is an important regulator of cranial suture during embryogenesis. Closure of the neural tube is achieved via Twist-triggered cellular transition from an epithelial to mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT), characterized by a remarkable increase in cell motility. In the absence of Twist activity, EMT and associated phenotypic changes in cell morphology and motility can also be induced, albeit moderately, by other transcription factor families, including Snail and Zeb. Aberrant EMT triggered by Twist in human mammary tumour cells was first reported to drive metastasis to the lung in a metastatic breast cancer model. Subsequent analysis of many types of carcinoma demonstrated overexpression of these unique EMT transcription factors, which statistically correlated with worse outcome, indicating their potential as biomarkers in the clinic. However, the mechanisms underlying their activation remain unclear. Interestingly, increasing evidence indicates they are selectively activated by distinct intracellular kinases, thereby acting as downstream effectors facilitating transduction of cytoplasmic signals into nucleus and reprogramming EMT and mesenchymal-epithelial transition (MET) transcription to control cell plasticity. Understanding these relationships and emerging data indicating differential phosphorylation of Twist leads to complex and even paradoxical functionalities, will be vital to unlocking their potential in clinical settings.

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