Cancer and Metastasis Reviews

, Volume 31, Issue 3–4, pp 469–478 | Cite as

Mesenchymal–epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer

  • N. P. A. Devika Gunasinghe
  • Alan Wells
  • Erik W. ThompsonEmail author
  • Honor J. Hugo


As yet, there is no cure for metastatic breast cancer. Historically, considerable research effort has been concentrated on understanding the processes of metastasis, how a primary tumour locally invades and systemically disseminates using the phenotypic switching mechanism of epithelial to mesenchymal transition (EMT); however, much less is understood about how metastases are then formed. Breast cancer metastases often look (and may even function) as ‘normal’ breast tissue, a bizarre observation against the backdrop of the organ structure of the lung, liver, bone or brain. Mesenchymal to epithelial transition (MET), the opposite of EMT, has been proposed as a mechanism for establishment of the metastatic neoplasm, leading to questions such as: Can MET be clearly demonstrated in vivo? What factors cause this phenotypic switch within the cancer cell? Are these signals/factors derived from the metastatic site (soil) or expressed by the cancer cells themselves (seed)? How do the cancer cells then grow into a detectable secondary tumour and further disseminate? And finally—Can we design and develop therapies that may combat this dissemination switch? This review aims to address these important questions by evaluating long-standing paradigms and novel emerging concepts in the field of epithelial mesencyhmal plasticity.


EMT MET Mesenchymal Epithelial Transition Breast cancer Metastasis Proliferation 



The authors wish to thank members of the Thompson and Wells laboratories for ideas and discussions which shaped the work and conception of this review and gratefully acknowledge the following sources of financial support: the National Breast Cancer Foundation, particularly the National Collaborative Research Program (EMPathy Breast Cancer Network) (Australia), Cancer Council Victoria, The Australian Government's Endeavour Awards Scholarship Program, the Victorian Government's Operational Infrastructure Support Program, the DoD CDMRP on Breast Cancer and the VA Merit Award Program, USA.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • N. P. A. Devika Gunasinghe
    • 1
    • 2
  • Alan Wells
    • 3
  • Erik W. Thompson
    • 1
    • 4
    Email author
  • Honor J. Hugo
    • 4
  1. 1.Department of Surgery, St. Vincent’s HospitalUniversity of MelbourneMelbourneAustralia
  2. 2.Department of Anatomy, Faculty of MedicineUniversity of PeradeniyaPeradeniyaSri Lanka
  3. 3.Department of PathologyUniversity of Pittsburgh and Pittsburgh VA Medical CenterPittsburghUSA
  4. 4.VBCRC Invasion and Metastasis UnitSt. Vincent’s InstituteMelbourneAustralia

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