Published online June 9, 2008
doi:10.1083/jcb.1816iti3
The Journal of Cell Biology, Vol. 181, No. 6, 875-
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Robinson
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IQGAP1 and exocyst component Sec8 colocalize at invadopodia.
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A secretory complex and a cytoskeletal polarity protein cooperate to make tumor cells more invasive, according to new work from Sakurai-Yageta et al.
To burrow into nearby tissue, tumor cells create membrane protrusions called invadopodia. Within invadopodia, vesicles accumulate that contain metalloproteinase enzymes needed to degrade the extracellular matrix. Because a secretory complex called the exocyst is known to link exocytic vesicles to growing membranes, the team tested the effect of depleting particular exocyst subunits in breast cancer cells. They showed that the cells were less able to degrade the matrix on which they were cultured and became less invasive.
The same subunits bound to a protein called IQGAP1, which links actin and microtubules at the leading edge of migrating cells, accumulate in invadopodia and have been implicated in tumor invasion. Linkage of IQGAP1 and the exocyst was needed for metalloproteinase accumulation at the invadopodia, though it remains to be determined whether the exocyst directly targets the vesicles. Two important promoters of actin cytoskeletal assembly, Cdc42 and RhoA, promoted the association of IQGAP1 with the exocyst, through direct contact with exocyst subunits. Knockdown of either Cdc42 or RhoA also reduced matrix degradation and tumor invasiveness.
The authors suggest that by linking IQGAP1 to the exocyst, the cell ensures coordination of two central features of tumor invasion: actin reorganization at the invadopodia and exocytosis of protein-degrading enzymes. 
Sakurai-Yageta, M., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200709076.[Abstract/Free Full Text]
Richard Robinson
rrobinson{at}nasw.org
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