PMID- 15122328 OWN - NLM STAT- MEDLINE DCOM- 20040721 LR - 20091119 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 23 IP - 30 DP - 2004 Jul 1 TI - Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis. PG - 5193-202 AB - 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. FAU - Lee, Chong-Chou AU - Lee CC AD - Van Andel Research Institute, 333 Bostwick Avenue, N.E., Grand Rapids, MI 49503, USA. FAU - Putnam, Andrew J AU - Putnam AJ FAU - Miranti, Cindy K AU - Miranti CK FAU - Gustafson, Margaret AU - Gustafson M FAU - Wang, Ling-Mei AU - Wang LM FAU - Vande Woude, George F AU - Vande Woude GF FAU - Gao, Chong-Feng AU - Gao CF LA - eng PT - Journal Article PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Drug Combinations) RN - 0 (HGF protein, human) RN - 0 (Laminin) RN - 0 (Luminescent Proteins) RN - 0 (Mitogens) RN - 0 (Nerve Tissue Proteins) RN - 0 (Proteoglycans) RN - 0 (Spry2 protein, rat) RN - 119978-18-6 (matrigel) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 9007-34-5 (Collagen) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Biosensing Techniques MH - Blotting, Western MH - Carcinoma, Renal Cell/metabolism/pathology MH - Cell Adhesion MH - *Cell Division MH - Cell Line, Tumor MH - *Cell Movement MH - Collagen/metabolism MH - Drug Combinations MH - Focal Adhesions MH - *Gene Expression Regulation, Neoplastic MH - Green Fluorescent Proteins MH - Hepatocyte Growth Factor/*metabolism/pharmacology MH - Humans MH - Laminin/metabolism MH - Leiomyosarcoma/metabolism/pathology MH - Luminescent Proteins/metabolism MH - Mitogens/*metabolism/pharmacology MH - Neoplasm Invasiveness MH - Nerve Tissue Proteins/*metabolism MH - Polyploidy MH - Proteoglycans/metabolism MH - Proto-Oncogene Proteins c-met/metabolism MH - Signal Transduction MH - Stress Fibers EDAT- 2004/05/04 05:00 MHDA- 2004/07/22 05:00 CRDT- 2004/05/04 05:00 PHST- 2004/05/04 05:00 [pubmed] PHST- 2004/07/22 05:00 [medline] PHST- 2004/05/04 05:00 [entrez] AID - 1207646 [pii] AID - 10.1038/sj.onc.1207646 [doi] PST - ppublish SO - Oncogene. 2004 Jul 1;23(30):5193-202. doi: 10.1038/sj.onc.1207646.