Abstract:
:Cell migration is an integral component of metastatic disease. The ability of cells to transit between mesenchymal and amoeboid modes of migration has complicated the development of successful therapies designed to target cell migration as a means of inhibiting metastasis. Therefore, investigations of the mechanisms that regulate cell migration and render cells stationary are necessary. Tropomyosins are actin-associating proteins that regulate the activity of several effectors of actin filament dynamics. Previously, we have shown that the tropomyosin isoform Tm5NM1 stabilizes actin filaments and inhibits cell migration in a two-dimensional culture system. Here, we show that Tm5NM1 inhibits the mesenchymal migration of multiple cell lines in an isoform-specific manner. Tm5NM1 stimulates the downregulation of Src kinase activity and a rounded or elliptical morphology in three-dimensional collagen gels, and cells have dramatically reduced capacity to form pseudopodia. Importantly, we find that Tm5NM1 inhibits both the mesenchymal to amoeboid and amoeboid to mesenchymal transitions. Collectively, our data suggest that mimicking the action of Tm5NM1 overexpression represents an approach for effectively inhibiting the mesenchymal mode of migration.
journal_name
Oncogenejournal_title
Oncogeneauthors
Lees JG,Bach CT,Bradbury P,Paul A,Gunning PW,O'Neill GMdoi
10.1038/onc.2010.516subject
Has Abstractpub_date
2011-03-10 00:00:00pages
1241-51issue
10eissn
0950-9232issn
1476-5594pii
onc2010516journal_volume
30pub_type
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