Cell-invasion events play crucial roles both in normal development and in human diseases such as metastatic cancer. SPARC/osteonectin is an extracellular matrix protein that has multiple functions in development and is overexpressed in a number of metastatic cancers including pancreatic, breast, and glioblastoma where it is associated with poor patient prognosis. The role of SPARC in promoting cancer progression remains poorly understood. The C. elegans
ost-1 gene encodes the worm ortholog of SPARC. A simple in vivo model of regulated cell invasion is the gonadal anchor cell (AC) invasion through basement membranes into the vulva epithelium during C. elegans larval development. We found that overexpression of SPARC promotes AC invasion in
fos-1(-) mutants (ortholog of proto-oncogene c-fos). In
fos-1(
ar105) mutants, the AC extends protrusions, but instead of passing through the basement membrane they are blocked and flatten there.
fos-1(
ar105) ACs fail to invade at the 4-cell stage and only 17% show partial invasion at the 8-cell stage. Strikingly, in three separate
fos-1(-);SPARC::GFP lines, SPARC overexpression suppressed the
fos-1(-) AC invasion defect. The ACs of a higher GFP expressing line (syIs113) invaded more often than ACs of a lower GFP expressing line (syIs110) suggesting that levels of SPARC overexpression are correlated with ability to promote AC invasion. The SPARC::GFP expression pattern in the
fos-1(-) background was unaffected by the loss of
fos-1 suggesting that SPARC is not a target of
fos-1 and the overexpression of SPARC has no apparent effects on AC invasion in otherwise wild-type animals. SPARC appears to have a unique ability to facilitate AC invasion as overexpression of other basement membrane proteins including fibulin and hemicentin does not promote AC invasion. To determine whether SPARC can promote AC invasion in other sensitized mutant backgrounds, we tested the ability of overexpression of SPARC to suppress the AC defect of
unc-6(
ev400) mutants. The
unc-6 gene encodes the C. elegans ortholog of the secreted guidance cue netrin. Consistent with a more general role for promoting invasion, overexpression of SPARC also suppressed the
unc-6(-) AC invasion defect. We hypothesize that SPARC may act 1) at the basement membrane to change its properties to facilitate passage through the membrane or 2) within the invasive AC to assist its innate invasive ability. This is the first in vivo evidence that SPARC directly promotes cell invasion and suggests that SPARC might facilitate metastasis by fostering invasion across basement membranes in cells that would normally be incapable of invasion.