Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis

Oncogene 23: 5193–5202, 2004.

Speaker：葉承昀

Commentator：蕭璦莉 老師

Time：13:00~14:00 ; October 13, 2004

Place：Room 601

Abstract：

Met, a proto-oncogene of receptor tyrosine kinase, can enhance the tumorgenesis.  Clinically, patients with Met overexpression have poor prognosis¹.  Hepatocyte growth factor/scatter factor (HGF/SF) is the ligand of Met.  Strict regulation of HGF/SF-Met signaling is essential for Met-related biological functions including cell proliferation, migration, invasion, and survival etc.  In this study, the authors demonstrated that HGF/SF-induced human Sprouty 2 (hSpry2) expression is a negative regulator in HGF/SF-Met signaling².  Spry protein was first identified in Drosophila as a feedback inhibitor of the FGF signaling pathway.  hSpry2 can also inhibit the FGFR-mediated Ras/MAPK signaling pathway, and inhibits cell proliferation, migration, differentiation.  Human leiomyosarcoma cell line SK-LMS-1 overexpression Spry2 transgene (SK-Spry2) was utilized to study Met-related biological functions.  Compared with SK-LMS-1, SK-Spry2 cells could inhibit HGF-mediated Met-related biological functions, including cell proliferation, anchorage-independent cell growth, migration and invasion.  In addition, electric cell-substrate impedance sensing assay confirmed that SK-Spry2 cell movement was restricted as compared to SK-LMS-1, indicating that Spry2 might facilitate cell attachment and spreading by enhancing focal adhesions and increasing forming of stress fibers.  FACS analysis of SK-Spry2 cell cycle showed that Spry2 resulted in G2/M accumulation and polyploidy.  All forgather, the authors suggest that HGF-induced Spry2 expression has negative influence on downstream of Met signaling as well as FGF and EGF receptors³.  The features revealed about make Spry2 suitable to be a tumor-suppressor protein.

References：

1.         Birchmeier, C., Birchmeier, W., Gherardi, E. & Vande Woude, G. F. Met, metastasis, motility and more. Nat Rev Mol Cell Biol 4, 915-25 (2003).

2.         Lee, C. C. et al. Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis. Oncogene 23, 5193-202 (2004).

3.         Guy, G. R. et al. Sprouty: how does the branch manager work? J Cell Sci 116, 3061-8 (2003).