Cell migration is fundamental to development and many cell types have a migratory phase during embryonic development when tissues and body structures are forming. Cancer metastasis is in many ways thought to be analogous to embryonic development. Some of the mechanisms that tumor cells use to hijack the adult body are thought to derive from their abilities to reactivate embryonic signaling and motility pathways and thus enhance their growth and motility. Melanomas are notorious for their ability to become highly invasive and metastatic if not removed early. While adult melanin producing cells, melanocytes, have limited mobility, melanoblasts are highly motile cells that move through the dermis and epidermis during embryogenesis and could serve as a useful paradigm for some aspects of melanoma invasion and metastasis. Recent findings from our laboratory using ex-vivo imaging of mouse melanoblast migration in the epidermis provide the first insights into the role of Rac1 in developing mouse melanoblasts in vivo. Melanoblasts do not move as a collective group, or use an invasive or blebbing mode of migration as revealed by other in vivo systems, but rather they extend short and long dynamic pseudopodia and squeeze between epidermal keratinocytes using myosin motors. Melanoblasts can initiate short actin-based protrusions independently of Rac1. Rac1 is required to control the rate of formation of long actin-based protrusions for effective translocation in skin. Our results reveal a novel mode of in vivo migration controlled by Rac1 that is important for normal development and likely in melanoma.
A Li, Y Ma, X Yu, RL Mort, CR Lindsay, D Stevenson, et al. Rac1 drives melanoblast organization during mouse development by orchestrating pseudopod-driven motility and cell-cycle progression. Dev Cell 2011; 21: 722- 34.
PMID: 21924960 DOI: 10.1016/j.devcel.2011.07.008