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

Jia, Dongya and Li, Xuefei and Bocci, Federico and Tripathi, Shubham and Deng, Youyuan and Jolly, Mohit Kumar and Onuchic, Jose N and Levine, Herbert (2019) Quantifying Cancer Epithelial-Mesenchymal Plasticity and its Association with Stemness and Immune Response. In: JOURNAL OF CLINICAL MEDICINE, 8 (5).

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Official URL: https://doi.org/10.3390/jcm8050725


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.

Item Type: Journal Article
Publisher: MDPI
Additional Information: The copyright for this article belongs to MDPI, ST ALBAN
Keywords: epithelial-mesenchymal transition; EMT spectrum; hybrid epithelial; mesenchymal phenotypes; CTC clusters; stemness; immune suppression; EMT metrics; systems biology
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 01 Aug 2019 11:01
Last Modified: 02 Aug 2019 04:30
URI: http://eprints.iisc.ac.in/id/eprint/63152

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