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

TitleCell motility in cancer invasion and metastasis: insights from simple model organisms.
Publication TypeJournal Article
Year of Publication2018
AuthorsStuelten CH, Parent CA, Montell DJ
JournalNat Rev Cancer
Volume18
Issue5
Pagination296-312
Date Published2018 May
ISSN1474-1768
Abstract

<p>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.</p>

DOI10.1038/nrc.2018.15
Alternate JournalNat. Rev. Cancer
PubMed ID29546880