1. Inhibitor of Growth 4 Suppresses Cell Spreading and Cell Migration by Interacting with a Novel Binding Partner, Liprin α1
- Author
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Motoko Unoki, Jiang Cheng Shen, Damien Ythier, Kensuke Kumamoto, Alain Duperray, Rémy Pedeux, Lyuba Varticovski, Curtis C. Harris, Duperray, Alain, Laboratory of Human Carcinogenesis, National Institutes of Health [Bethesda] (NIH), Groupe de Recherche Sur Le Cancer du Poumon : Bases Moléculaires de la Progression Tumorale, Dépistage et Thérapie Génique, and Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Cancer Research ,MESH: Cell Line, Tumor ,Motility ,Cell Cycle Proteins ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Transfection ,Article ,MESH: Glioma ,Cell membrane ,MESH: Cell Cycle Proteins ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Movement ,Cell Line, Tumor ,MESH: RNA, Small Interfering ,MESH: Homeodomain Proteins ,medicine ,Humans ,MESH: Protein Binding ,MESH: Tumor Suppressor Proteins ,RNA, Small Interfering ,Cell Cycle Protein ,MESH: Cell Movement ,Adaptor Proteins, Signal Transducing ,MESH: Adaptor Proteins, Signal Transducing ,Homeodomain Proteins ,MESH: Colonic Neoplasms ,MESH: Humans ,biology ,Cell growth ,Tumor Suppressor Proteins ,MESH: Transfection ,Cell Membrane ,Cell migration ,Glioma ,Vinculin ,Cell biology ,medicine.anatomical_structure ,Oncology ,Cytoplasm ,Colonic Neoplasms ,biology.protein ,Lamellipodium ,Protein Binding ,MESH: Cell Membrane - Abstract
Inhibitor of growth 4 (ING4) is a candidate tumor suppressor that plays a major role in gene regulation, cell cycle control, apoptosis, and angiogenesis. ING4 expression is down-regulated in glioblastoma cells and head and neck squamous cell carcinoma. Here, we identified liprin α1/PPFIA1, a cytoplasmic protein necessary for focal adhesion formation and axon guidance, as a novel interacting protein with ING4. ING4 and liprin α1 colocalized at lamellipodia in the vicinity of vinculin. Overexpressed ING4 suppressed cell spreading and cell migration. In contrast, overexpressed liprin α1 enhanced cell spreading and cell migration. Knockdown of endogenous ING4 with RNA interference induced cell motility, whereas knockdown of endogenous liprin α1 suppressed cell motility. ING4 also suppressed cell motility that was enhanced by liprin α1. However, ING4 did not further suppress cell motility when liprin α1 was suppressed with RNA interference, suggesting a functional and mechanistic interdependence between these proteins. In addition to its nuclear functions, cytoplasmic ING4 interacts with liprin α1 to regulate cell migration and, with its known antiangiogenic function, may prevent invasion and metastasis. [Cancer Res 2007;67(6):2552–8]
- Published
- 2007
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