Figure 9

Graphical abstract of the Snail and MMP-9 signaling axis in facilitating a neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP-9) cross-talk in regulating receptor tyrosine kinases (RTKs) in ovarian cancer cells to promote tumor neovascularization. Notes: For ovarian cancers, Snail and MMP-9 expressions are closely connected in similar invasive tumor processes. Snail induces MMP-9 secretion via multiple signaling pathways, but particularly in cooperation with oncogenic H-Ras (RasV12), Snail leads to the transcriptional up-regulation of MMP-9. This Snail-MMP-9 signaling axis is the connecting link in promoting growth factor receptor glycosylation modification involving the subsequent receptor-signaling platform of a Neu1-MMP-9 crosstalk tethered at the ectodomain of RTKs. Activated MMP-9 is proposed to remove the elastin-binding protein (EBP) as part of the molecular multi-enzymatic complex that contains β-galactosidase/Neu1 and protective protein cathepsin A (PPCA). Activated Neu1 hydrolyzes α-2,3-sialic acid residues of RTKs at the ectodomain to remove steric hindrance to receptor association and activation. This process sets the stage for Snail's role in tumor neovascularization. Abbreviations: GPCR, G-protein coupled receptor; Pi3K, phosphatidylinositol 3-kinase; GTP, guanine triphosphate; EBP, elastin binding protein; PPCA, protective protein cathepsin A. Citation: Taken in part from Research and Reports in Biochemistry 2013:3 17-30. © 2013 Abdulkhalek et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted non-commercial use, provided the original work is properly cited.