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Nat Rev Cancer. 2018 May;18(5):296-312. doi: 10.1038/nrc.2018.15. Epub 2018 Mar 16.

Cell motility in cancer invasion and metastasis: insights from simple model organisms.

Author information

1
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.
2
Department of Pharmacology, Michigan Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
3
Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA, USA.

Abstract

Metastasis remains the greatest challenge in the clinical management of cancer. Cell motility is a fundamental and ancient cellular behaviour that contributes to metastasis and is conserved in simple organisms. In this Review, we evaluate insights relevant to human cancer that are derived from the study of cell motility in non-mammalian model organisms. Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio permit direct observation of cells moving in complex native environments and lend themselves to large-scale genetic and pharmacological screening. We highlight insights derived from each of these organisms, including the detailed signalling network that governs chemotaxis towards chemokines; a novel mechanism of basement membrane invasion; the positive role of E-cadherin in collective direction-sensing; the identification and optimization of kinase inhibitors for metastatic thyroid cancer on the basis of work in flies; and the value of zebrafish for live imaging, especially of vascular remodelling and interactions between tumour cells and host tissues. While the motility of tumour cells and certain host cells promotes metastatic spread, the motility of tumour-reactive T cells likely increases their antitumour effects. Therefore, it is important to elucidate the mechanisms underlying all types of cell motility, with the ultimate goal of identifying combination therapies that will increase the motility of beneficial cells and block the spread of harmful cells.

PMID:
29546880
PMCID:
PMC6790333
DOI:
10.1038/nrc.2018.15
[Indexed for MEDLINE]
Free PMC Article

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