Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis.
A strict regulation of hepatocyte growth factor/scatter factor (HGF/SF)-Met signaling is essential for its appropriate function. Several negative regulators of Met signaling have been identified. Here we report that human Spry2 is induced by HGF/SF and negatively regulates HGF/SF-Met signaling. We show that overexpression of Spry2 inhibits cell proliferation, anchorage-independent cell growth, and migration in wound-healing and in vitro invasion assays. Measured in an electric cell-substrate impedance sensing biosensor, cell movement is restricted, because Spry2 dramatically facilitates cell attachment and spreading by enhancing focal adhesions and increasing stress fibers. An analysis of cell cycle distribution shows, unexpectedly, that Spry2-GFP cells are polyploid. Thus, as with FGF and EGF receptors, Spry2-GFP tempers downstream Met signaling in addition to its pronounced effect on cell adhesion, and it has properties suitable to be considered a tumor-suppressor protein.
Lee
Chong-Chou
CC
Van Andel Research Institute, 333 Bostwick Avenue, N.E., Grand Rapids, MI 49503, USA.
Putnam
Andrew J
AJ
Miranti
Cindy K
CK
Gustafson
Margaret
M
Wang
Ling-Mei
LM
Vande Woude
George F
GF
Gao
Chong-Feng
CF
D015374:Biosensing Techniques; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D022001:Focal Adhesions; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000378:metabolism; D007890:Leiomyosarcoma / Q000378:metabolism / Q000473:pathology; D008164:Luminescent Proteins / Q000378:metabolism; D008934:Mitogens / Q000378:metabolism* / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011123:Polyploidy; D011509:Proteoglycans / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015398:Signal Transduction; D022502:Stress Fibers
D004338:Drug Combinations; C066855:HGF protein, human; D007797:Laminin; D008164:Luminescent Proteins; D008934:Mitogens; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; C404992:Spry2 protein, rat; C059485:matrigel; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; D003094:Collagen; D019859:Proto-Oncogene Proteins c-met