Clinical & Experimental Metastasis

, Volume 35, Issue 4, pp 285–308 | Cite as

The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome

  • Andrew D. Redfern
  • Lisa J. Spalding
  • Erik W. Thompson
Research Paper


Epithelial mesenchymal transition (EMT) describes the shift of cells from an epithelial form to a contact independent, migratory, mesenchymal form. In cancer the change is linked to invasion and metastasis. Tumour conditions, including hypoxia, acidosis and a range of treatments can trigger EMT, which is implicated in the subsequent development of resistance to those same treatments. Consequently, the degree to which EMT occurs may underpin the entire course of tumour progression and treatment response in a patient. In this review we look past the protective effect of EMT against the initial treatment, to the role of the mesenchymal state, once triggered, in promoting disease growth, spread and future treatment insensitivity. In patients a correlation was found between the propensity of a treatment to induce EMT and failure of that treatment to provide a survival benefit, implicating EMT induction in accelerated tumour progression after treatment cessation. Looking to the mechanisms driving this detrimental effect; increased proliferation, suppressed apoptosis, stem cell induction, augmented angiogenesis, enhanced metastatic dissemination, and immune tolerance, can all result from treatment-induced EMT and could worsen outcome. Evidence also suggests EMT induction with earlier therapies attenuates benefits of later treatments. Looking beyond epithelial tumours, de-differentiation also has therapy-attenuating effects and reversal thereof may yield similar rewards. A range of potential therapies are in development that may address the diverse mechanisms and molecular control systems involved in EMT-induced accelerated progression. Considering the broad reaching effects of mesenchymal shift identified, successful deployment of such treatments could substantially improve patient outcomes.


Epithelial mesenchymal transition Resistance Metastasis Treatment Proliferation Apoptosis 



Aldehyde dehydrogenase 1


Anaplastic lymphoma kinase


All-trans retinoic acid


Chemokine ligand 2


Clustered regulatory interspaced short palindromic repeats


Cancer stem cells


Circulating tumour cells


Cytotoxic T-lymphocyte–associated antigen 4


Epidermal growth factor


EMT-inhibiting sextet


Epithelial-mesenchymal axis


Epithelial-mesenchymal plasticity


Epithelial mesenchymal transition


EMT-transcriptional factors


Estrogen receptor alpha


Extracellular signal-regulated kinase


Hepatocellular carcinoma


Histone deacetylase


Human epidermal growth factor receptor 2


Hypoxia inducible factor-1α


Inhibitor of apoptosis


Mitogen activated protein kinase


Mitogen-activated protein/extracellular signal-regulated kinase kinase


Mesenchymal epithelial transition




Matrix metalloproteinase


Nuclear factor kB


Non-small cell lung cancer


Overall survival


Programmed death 1


Programmed death ligand 1


Progression-free survival


Transforming growth factor beta


Vascular endothelial growth factor


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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of MedicineUniversity of Western Australia (UWA)MurdochAustralia
  2. 2.Institute of Health and Biomedical Innovation and School of Biomedical SciencesQueensland University of Technology (QUT)BrisbaneAustralia
  3. 3.Translational Research InstituteWoolloongabbaAustralia
  4. 4.Department of SurgeryUniversity of MelbourneMelbourneAustralia

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