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Cell Heterogeneity and Phenotypic Plasticity in Metastasis Formation: The Case of Colon Cancer

Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
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Author to whom correspondence should be addressed.
Cancers 2019, 11(9), 1368; https://doi.org/10.3390/cancers11091368
Received: 25 July 2019 / Revised: 9 September 2019 / Accepted: 11 September 2019 / Published: 14 September 2019
(This article belongs to the Special Issue Metastatic Progression and Tumour Heterogeneity)
The adenoma-to-carcinoma progression in colon cancer is driven by a sequential accumulation of genetic alterations at specific tumor suppressors and oncogenes. In contrast, the multistage route from the primary site to metastasis formation is underlined by phenotypic plasticity, i.e., the capacity of disseminated tumor cells to undergo transiently and reversible transformations in order to adapt to the ever-changing environmental contexts. Notwithstanding the considerable body of evidence in support of the role played by epithelial-to-mesenchymal transition (EMT)/mesenchymal-to-epithelial transition (MET) in metastasis, its rate-limiting function, the detailed underlying cellular and molecular mechanisms, and the extension of the necessary morphologic and epigenetic changes are still a matter of debate. Rather than leading to a complete epithelial or mesenchymal state, the EMT/MET-program generates migrating cancer cells displaying intermediate phenotypes featuring both epithelial and mesenchymal characteristics. In this review, we will address the role of colon cancer heterogeneity and phenotypic plasticity in metastasis formation and the contribution of EMT to these processes. The alleged role of hybrid epithelial/mesenchymal (E/M) in collective and/or single-cell migration during local dissemination at the primary site and more systemic spreading will also be highlighted. View Full-Text
Keywords: colon cancer; Wnt signaling; tumor heterogeneity; phenotypic plasticity; EMT; hybrid E/M; collective and single-cell migration; beta-catenin paradox colon cancer; Wnt signaling; tumor heterogeneity; phenotypic plasticity; EMT; hybrid E/M; collective and single-cell migration; beta-catenin paradox
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Teeuwssen, M.; Fodde, R. Cell Heterogeneity and Phenotypic Plasticity in Metastasis Formation: The Case of Colon Cancer. Cancers 2019, 11, 1368.

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