We have previously performed an unbiased screen to identify genes whose expression is associated with the metastatic phenotype. Secondary screening of these genes using custom microarray chips identified ASAP1, a multi-domain adaptor
protein with
ADP-ribosylation factor-GAP activity, as being potentially involved in
tumor progression. Here, we show that at least three different splice forms of ASAP1 are upregulated in rodent
tumor models in a manner that correlates with metastatic potential. In human
cancers, we found that ASAP1 expression is strongly upregulated in a variety of
tumors in comparison with normal tissue and that this expression correlates with poor
metastasis-free survival and prognosis in
colorectal cancer patients. Using loss and gain of function approaches, we were able to show that ASAP1 promotes
metastasis formation in vivo and stimulates
tumor cell motility, invasiveness, and adhesiveness in vitro. Furthermore, we show that ASAP1 interacts with the
metastasis-promoting
protein h-prune and stimulates its
phosphodiesterase activity. In addition, ASAP1 binds to the SH3 domains of several
proteins, including SLK with which it co-immunoprecipitates. These data support the notion that ASAP1 can contribute to the dissemination of a variety of
tumor types and represent a potential target for
cancer therapy.