Trends in Cell Biology
Research updateRECKing MMP function: implications for cancer development
Section snippets
Regulation of matrix metalloproteinases
The MMP family comprises ∼24 members and the closely related ADAMS and ADAMTS proteases characterized in humans, rodents and amphibians [3]. Initially classified as zinc-dependent proteases capable of cleaving all structural components of the ECM (in vitro), their specific proteolytic targets have since expanded to include other extracellular proteins. These include ECM molecules, other proteases, protease inhibitors, clotting factors, chemotactic molecules, latent growth factors, growth-factor
RECK and MMP inhibition
RECK, originally discovered in an expression cloning screen attempting to isolate human cDNAs inducing flat reversion of v-Ki-ras-transformed NIH3T3 cells [12], encodes a secreted 110-kDa glycoprotein containing a serine-protease inhibitor-like domain, two domains containing epidermal growth factor (EGF)-like repeats and a C-terminal domain encoding a glycosylphosphatidylinositol (GPI) modification anchoring RECK to the plasma membrane [13]. RECK (‘version-inducing-steine-rich protein with
Therapeutic implications for RECK in neoplastic progression
The combined demonstrations that RECK expression is low in many human tumors and that RECK expression reduces invasive and metastatic behavior of neoplastic cells, in combination with its demonstrated role as a multifaceted MMP inhibitor invite the speculation that RECK might have therapeutic utility. One observation in support of this is the effective MMP-inhibitory activities of soluble RECK – pharmacologically appealing in that delivery would not be problematic if stability could be achieved
Acknowledgements
We thank Zena Werb and Leon van Kempen for helpful discussions. We apologize to authors whose work could not be cited owing to space limitations. L.M.C. is supported by the NIH, AACR, the V Foundation for Cancer Research, the Edward G. Mallinckrodt Foundation and the California Research Coordinating Committee.
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2016, Journal of Lipid ResearchCitation Excerpt :Though the mechanism used by GDE2 to inhibit Notch signaling cannot be explained by conventional GDPD activity, the GPI-AP-releasing (GPIase) activity of GDE2 promotes this process during neural differentiation (5). Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a GPI-AP that activates Notch signaling in cortical progenitors by directly inhibiting ADAM10, a disintegrin, and metallopeptidase 10, which removes the Notch ligand Delta-like 1 (DLL1) (65–67). GDE2's GPIase activity is derived from the GDPD activity domain, which sheds the GPI anchor of RECK in a manner different from that of GPI-PLD (5) (Table 1).
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