One of the key steps in cancer progression is the metastasis of carcinoma cells from the primary tumour. This process involves invasive cell migration, which requires the formation of actin-rich protrusions at the leading edge of migrating cells. An actin-regulatory protein that is upregulated in several human cancers is Mena, a member of the Ena/VASP family. Overexpression of Mena in rat breast carcinoma cells increases metastasis to the lungs. However, current understanding of Ena/VASP protein function comes mainly from in vitro studies of fibroblasts, in which overexpression of Mena decreases rather than increases cell migration speeds. It has therefore been unclear what effect the overexpression of Ena/VASP proteins might have in an in vivo setting.
In this study, the authors investigate how altering the levels of Ena, the sole Drosophila Ena/VASP family member, affects the migration of macrophages (haemocytes) through the embryo during development, a process that is similar in many respects to tumour-cell migration. Using detailed analysis of the actin protrusions formed by the macrophages, the authors show that inactivation of Ena results in the formation of stable protrusions, whereas Ena overexpression results in very dynamic protrusions, revealing that Ena is a key regulator of lamellipodial dynamics in Drosophila macrophages, as has been observed for fibroblasts in vitro. However, although overexpression of Mena reduces fibroblast migration speeds in vitro, the authors show here that Ena overexpression increases macrophage migration speeds in the embryo, consistent with previous findings that Mena overexpression increases cell motility and metastasis in breast cancer. The authors also provide evidence that the difference in results obtained between in vivo and in vitro systems might be attributed to the difference in spatial constraints experienced by cells in vivo.
Implications and future directions
This paper provides insight into how increased Mena levels might contribute to cell motility and metastasis, and illustrates the importance of investigating cell migration in a living organism. In addition, this system should prove useful for determining the contribution of other actin regulators to cell migration in vivo, which might help to better understand how dysregulation of the actin cytoskeleton promotes metastasis and cancer progression.
- © 2011. Published by The Company of Biologists Ltd
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