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Review

Quantifying Cancer Epithelial-Mesenchymal Plasticity and its Association with Stemness and Immune Response

1
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA
2
Department of Chemistry, Rice University, Houston, TX 77005, USA
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PhD Program in Systems, Synthetic, and Physical Biology, Rice University, Houston, TX 77005, USA
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Applied Physics Graduate Program, Rice University, Houston, TX 77005, USA
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Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India
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Department of Biosciences, Rice University, Houston, TX 77005, USA
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Department of Physics and Astronomy, Rice University, Houston, TX 77005, USA
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Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
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Department of Physics, Northeastern University, Boston, MA 02115, USA
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(5), 725; https://doi.org/10.3390/jcm8050725
Received: 16 April 2019 / Revised: 14 May 2019 / Accepted: 20 May 2019 / Published: 22 May 2019
Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial–mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e., the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression. View Full-Text
Keywords: epithelial–mesenchymal transition; EMT spectrum; hybrid epithelial/mesenchymal phenotypes; CTC clusters; stemness; immune suppression; EMT metrics; systems biology epithelial–mesenchymal transition; EMT spectrum; hybrid epithelial/mesenchymal phenotypes; CTC clusters; stemness; immune suppression; EMT metrics; systems biology
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MDPI and ACS Style

Jia, D.; Li, X.; Bocci, F.; Tripathi, S.; Deng, Y.; Jolly, M.K.; Onuchic, J.N.; Levine, H. Quantifying Cancer Epithelial-Mesenchymal Plasticity and its Association with Stemness and Immune Response. J. Clin. Med. 2019, 8, 725. https://doi.org/10.3390/jcm8050725

AMA Style

Jia D, Li X, Bocci F, Tripathi S, Deng Y, Jolly MK, Onuchic JN, Levine H. Quantifying Cancer Epithelial-Mesenchymal Plasticity and its Association with Stemness and Immune Response. Journal of Clinical Medicine. 2019; 8(5):725. https://doi.org/10.3390/jcm8050725

Chicago/Turabian Style

Jia, Dongya, Xuefei Li, Federico Bocci, Shubham Tripathi, Youyuan Deng, Mohit K. Jolly, José N. Onuchic, and Herbert Levine. 2019. "Quantifying Cancer Epithelial-Mesenchymal Plasticity and its Association with Stemness and Immune Response" Journal of Clinical Medicine 8, no. 5: 725. https://doi.org/10.3390/jcm8050725

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