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Journal of Cancer Research and Clinical Oncology

, Volume 141, Issue 2, pp 189–201 | Cite as

The biological and clinical importance of epithelial–mesenchymal transition in circulating tumor cells

  • Huiying Liu
  • Xiaofeng Zhang
  • Jun Li
  • Bin Sun
  • Haihua Qian
  • Zhengfeng Yin
Review – Cancer Research

Abstract

Movement of tumor cells from a primary tumor to a nonadjacent or distant site is a contiguous and complex process. Among the multiple natural cellular programs that promote initiation and progression of tumor metastasis, epithelial–mesenchymal transition (EMT) may play a key role in the ultimate generation of a metastatic foci. Acquisition of the EMT phenotype by tumor cells not only increases their migration and invasion potentials, thereby facilitating their ability to infiltrate blood vessels and to produce circulating tumor cells (CTCs), but also promotes survival of CTCs in the bloodstream and their ability to extravasate out of the circulatory system and invade proximal tissues. In organs distal to the primary tumor, the phenotypic switching mechanism of mesenchymal–epithelial transition (MET) enables CTCs to grow and colonize, enhancing the likelihood of establishing metastasis. In addition, CTCs that have undergone EMT attain increased resistance to chemotherapy and targeted therapy. CTCs with the EMT phenotype have become recognized as an active source of metastases, and targeting EMT/MET processes during the individual steps of tumor metastasis represents a promising new approach for alleviating cancer metastasis and recurrence. In this article, we focus on the biological and clinical importance of EMT and/or MET in CTCs during the individual steps of tumor metastasis, summarizing the recent findings of the regulatory roles played by EMT and/or MET in the generation, survival, and recolonization of CTCs and discussing the EMT-targeting strategies developed for tumor diagnosis as well as their potential for management of metastatic malignant diseases.

Keywords

Epithelial–mesenchymal transition (EMT) Mesenchymal–epithelial transition (MET) Circulating tumor cells (CTCs) Metastasis 

Notes

Acknowledgments

This work was supported by Grants from the China National Key Projects for Infectious Disease (No. 2012ZX10002012-10), the National Nature Science Foundation of China (Nos. 81172207, 81272668, 81272669, and 81301830), and the National High-Tech Research and Development Program of China (No. 2007AA02Z461).

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Huiying Liu
    • 1
  • Xiaofeng Zhang
    • 1
  • Jun Li
    • 1
  • Bin Sun
    • 1
  • Haihua Qian
    • 1
  • Zhengfeng Yin
    • 1
  1. 1.Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiChina

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