NDLI: Downregulation of Skp2 inhibits the growth and metastasis of gastric cancer cells in vitro and in vivo.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wei, Zheng Jiang, Xian Liu, Fengjun Qiao, Haiquan Zhou, Baoguo Zhai, Bo Zhang, Lianfeng Zhang, Xuwen Han, Likun Jiang, Hongchi Krissansen, Geoffrey W. Sun, Xueying
Description	Country affiliation: China Author Affiliation: Wei Z ( The Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.)
Abstract	S-phase kinase-associated protein-2 (Skp2) is overexpressed in human cancers and associated with poor prognosis. Skp2 acts as an oncogenic protein by enhancing cancer cell growth and tumor metastasis. The present study has demonstrated that small hairpin RNA (shRNA)-mediated downregulation of Skp2 markedly inhibits the viability, proliferation, colony formation, migration, invasion, and apoptosis of human gastric cancer MGC803 cells, which express a high level of Skp2. In contrast, Skp2 shRNA had only a slight effect on the above properties of BGC823 cells, which express a low level of Skp2. In accord, knockdown of Skp2 suppressed the ability of MGC803 cells to form tumors and to metastasize to the lungs of mice, and the growth of established tumors, by inhibiting cell proliferation and enhancing cell apoptosis. In contrast, overexpression of Skp2 promoted tumorigenesis of BGC823 cells in mice. Skp2 depletion induced cell cycle arrest in the G(1)/S phase by upregulating p27, p21, and p57 and downregulating cyclin E and cyclin-dependent kinase 2. Skp2 depletion also increased caspase-3 activity, impeded the ability of cells to form filopoidia and locomote, upregulated RECK (reversion-inducing cysteine-rich protein with kazal motifs), and downregulated matrix metalloproteinase (MMP)-2 and MMP-9 activity and expression. The results suggest that downregulating Skp2 warrants investigation as a promising strategy to treat gastric cancers that express high levels of Skp2.
File Format	HTM / HTML
ISSN	10104283
Issue Number	1
Volume Number	34
e-ISSN	14230380
Journal	Tumor Biology
Language	English
Publisher	Springer
Publisher Date	2013-02-01
Publisher Place	Netherlands
Access Restriction	Subscribed
Subject Keyword	Discipline Medicine__semicolon__oncology S-phase Kinase-associated Proteins Metabolism Stomach Neoplasms Pathology Animals Apoptosis Caspase 3 Biosynthesis Cell Cycle Checkpoints Cell Line, Tumor Cell Movement Cell Proliferation Cyclin E Cyclin-dependent Kinase 2 Cyclin-dependent Kinase Inhibitor P21 Cyclin-dependent Kinase Inhibitor P27 Cyclin-dependent Kinase Inhibitor P57 Down-regulation Gpi-linked Proteins Humans Male Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Mice Mice, Inbred Balb C Mice, Nude Neoplasm Invasiveness Neoplasm Metastasis Rna Interference Rna, Small Interfering Genetics Up-regulation Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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