Tumor Biology

, Volume 34, Issue 4, pp 2019–2030 | Cite as

Crosstalk between breast cancer stem cells and metastatic niche: emerging molecular metastasis pathway?

  • Hassan Fazilaty
  • Mossa Gardaneh
  • Tayyeb Bahrami
  • Arash Salmaninejad
  • Babak Behnam


Metastatic colonization represents the final step of metastasis, and is the major cause of cancer mortality. Metastasis as an “inefficient” process requires the right population of tumor cells in a suitable microenvironment to form secondary tumors. Cancer stem cells are the only capable population of tumor cells to progress to overt metastasis. On the other hand, the occurrence of appropriate microenvironmental conditions within the target tissue would be critical for metastasis formation. Metastatic niche seems to be the specialized microenvironment to support tumor initiating cells at the distant organ. Master regulators not only determine cancer stem cell state, but also may have regulatory roles in metastatic niche elements. Meanwhile, both cancer stem cell and metastatic niche may function like two sides of the metastatic coin. Hypoxia inducible factors have multiple roles in regulation of both sides of this coin. TGF-β superfamily, also, have been considered as master regulators of epithelial to mesenchymal transition and metastasis and may play crucial roles in regulation of metastatic niche as well. In this regard, we hypothesize the presence of a possible emerging molecular pathway in the biological process of breast cancer metastasis. In this process, non-Smad TGF-β-induced metastasis connects cancer stem cell and metastatic niche formation through a central path, “Metastasis Pathway”.


Molecular metastasis pathway Cancer stem cell Metastatic niche Breast cancer metastasis TGF-β Epithelial to mesenchymal transition 



The authors would like to thank Dr. Don X. Nguyen for critical review, and also thank Dr. Shirin Saeidi and Mr. Behnam Bakhtiarian for critical reading of the manuscript.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Hassan Fazilaty
    • 1
  • Mossa Gardaneh
    • 2
  • Tayyeb Bahrami
    • 1
  • Arash Salmaninejad
    • 1
  • Babak Behnam
    • 3
  1. 1.Department of Medical Genetics, Faculty of MedicineTehran University of Medical Sciences (TUMS)TehranIran
  2. 2.Department of Molecular GeneticsNational Institute of Genetic Engineering and Biotechnology (NIGEB)TehranIran
  3. 3.Department of Medical Genetics and Molecular Biology, Faculty of MedicineIran University of Medical Sciences (IUMS)TehranIran

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