The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA
J Cell Biol.. 2008 Jun 16; 181(6): 985-98
DOI: jcb.200709076 [pii]10.1083/jcb.200709076
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Invadopodia are actin-based membrane protrusions formed at contact sites between
invasive tumor cells and the extracellular matrix with matrix proteolytic
activity. Actin regulatory proteins participate in invadopodia formation, whereas
matrix degradation requires metalloproteinases (MMPs) targeted to invadopodia. In
this study, we show that the vesicle-tethering exocyst complex is required for
matrix proteolysis and invasion of breast carcinoma cells. We demonstrate that
the exocyst subunits Sec3 and Sec8 interact with the polarity protein IQGAP1 and
that this interaction is triggered by active Cdc42 and RhoA, which are essential
for matrix degradation. Interaction between IQGAP1 and the exocyst is necessary
for invadopodia activity because enhancement of matrix degradation induced by the
expression of IQGAP1 is lost upon deletion of the exocyst-binding site. We
further show that the exocyst and IQGAP1 are required for the accumulation of
cell surface membrane type 1 MMP at invadopodia. Based on these results, we
propose that invadopodia function in tumor cells relies on the coordination of
cytoskeletal assembly and exocytosis downstream of Rho guanosine triphosphatases.
DOI: 10.1083/jcb.200709076
PMCID: PMC2426946
PMID: 18541705 [Indexed for MEDLINE]