Involvement of the Paxillin Pathway in Jb6 Cl41 Cell Transformation.
From: Hormel Institute, University of Minnesota, Austin, Minnesota.
Cancer research
- Publish Date: Jun 2006
- ISSN: 0008-5472
- Volume: 66
- Issue: 11
- Pages: 5968-74
- Medium: Print
- Language: English
- Citation (JAMA): Tatsumi Yasuaki, Cho Yong-Yeon, He Zhiwei, et al. Involvement of the Paxillin Pathway in Jb6 Cl41 Cell Transformation.. Cancer Res. Jun 2006;66:5968-74
Abstract
Paxillin is a substrate of the Src tyrosine onco-kinase and is involved in cell transformation, cell spreading, migration, and cancer development mediated through the mitogen-activated protein kinase signaling cascades. Here, we showed that paxillin plays a key role in skin cell transformation induced by epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA). To investigate the mechanism of paxillin’s role in cell transformation, we established a paxillin knockdown stably transfected cell line by introducing small interfering RNA-paxillin (si-paxillin). The si-paxillin cells displayed a dramatic suppression of cell proliferation and anchorage-independent cell transformation induced by EGF or TPA compared with si-mock control cells. In si-paxillin cells, decreased activator protein-1 (AP-1)-dependent luciferase activity corresponded with suppressed AP-1 DNA binding activity. Importantly, knockdown of paxillin inhibited EGF- or TPA-induced c-Jun phosphorylation at Ser(63) and Ser(73). Furthermore, total c-Jun protein level was dramatically decreased in si-paxillin cells and was dependent on serum deprivation time. The down-regulation of c-Jun was restored in si-paxillin cells by treatment with the proteasome inhibitor lactacystin but not by the lysosome inhibitor leupeptin. These results clearly provided evidence that paxillin regulates c-Jun protein level and plays a key role in cell transformation most likely through the regulation of c-Jun stability.
Mesh Headings (Keywords): Animals, Base Sequence, Cell Growth Processes, Cell Line, Cell Transformation, Neoplastic, Down-Regulation, Epidermal Growth Factor, MAP Kinase Kinase 4, Mice, Molecular Sequence Data, Paxillin, Phosphorylation, Proto-Oncogene Proteins c-jun, RNA, Small Interfering, Serine, Skin, Skin Neoplasms, Tetradecanoylphorbol Acetate, Transfection
Check for Full Text / PubMed Unique Identifier (PMID): 16740738
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