SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane
Fig 1
SPARC overexpression promotes AC invasion.
(A) A schematic diagram of AC invasion. The AC (blue) breaches the BM (magenta) after the vulval precursor cell P6.p (dark grey) has divided once (P6.p two-cell stage), and completely clears the BM separating the AC and the vulval cells before a second round of P6.p divisions (P6.p four-cell stage). The vulval cells (grey) continue to divide and invaginate (P6.p eight-cell stage). (B) A schematic diagram depicts the major signaling pathways regulating AC invasion. FOS-1A regulates transcription of several pro-invasive genes. Integrin (purple) and netrin (beige) signaling promote F-actin-mediated invasive machinery formation. The vulval cells send an unidentified cue to the AC (absent in lin-3(n1059)/lin-3(n378) mutants lacking specification of the vulval cell fate) to stimulate invasion. (C) Representative DIC images overlaid with laminin::GFP fluorescence (magenta) show successful AC (white arrow head) invasion in a wild type animal (top panels); failure of AC invasion in a fos-1(ar105) animal (middle); and rescued invasion in a fos-1(ar105); SPARC overexpression (o/e; syIs113) animal (lower). (D) The graph depicts the frequency of AC-initiated BM breach at the P6.p eight-cell stage in animals with mutations in different aspects of the AC invasion program with and without SPARC overexpression (syIs113; n≥48 for each condition). Error bars show 95% confidence intervals with a continuity correction. * denotes p<0.05, ** denotes p<0.005, and *** denotes p<0.0005 by two-tailed Fisher’s exact test. Scale bar denotes 5 μm.