Inhibitor of growth 4 suppresses cell spreading and cell migration by interacting with a novel binding partner, liprin α1
Inhibitor of growth 4 suppresses cell spreading and cell migration by interacting with a novel binding partner, liprin α1
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DOI：
10.1158/0008-5472.can-06-3870
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发表时间：
2007-03-15
期刊：
影响因子：
11.2
通讯作者：
Harris, Curtis C.
中科院分区：
文献类型：
--
作者：
Shen, Jiang-Cheng;Unoki, Motoko;Harris, Curtis C.
生长抑制因子4（Inhibitor of growth 4，ING 4）是一种重要的肿瘤抑制因子，在基因调控、细胞周期调控、细胞凋亡和血管生成中发挥重要作用。ING 4在胶质母细胞瘤细胞和头颈部鳞状细胞癌中表达下调。在这里，我们确定了脂蛋白α 1/PPFIA 1，一种细胞质蛋白质所必需的粘着斑形成和轴突的指导，作为一种新的相互作用蛋白质ING 4。ING 4和liprin α 1共定位于黏着斑蛋白附近的板状伪足。过表达ING 4抑制细胞铺展和细胞迁移。相反，过表达的liprin α 1增强细胞的扩散和细胞迁移。用RNA干扰敲低内源性ING 4诱导细胞运动，而敲低内源性Liprin α 1抑制细胞运动。ING 4也抑制细胞运动，这是由liprin α 1增强。然而，ING 4没有进一步抑制细胞运动时，Liprin α 1被抑制RNA干扰，这表明这些蛋白质之间的功能和机制的相互依赖性。除了其核功能外，胞质ING 4与liprin α 1相互作用以调节细胞迁移，并具有已知的抗血管生成功能，可防止侵袭和转移。
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 alpha 1/PPFIA1, a cytoplasmic protein necessary for focal adhesion formation and axon guidance, as a novel interacting protein with ING4. ING4 and liprin alpha 1 colocalized at lamellipodia in the vicinity of vinculin. Overexpressed ING4 suppressed cell spreading and cell migration. In contrast, overexpressed liprin alpha 1 enhanced cell spreading and cell migration. Knockdown of endogenous ING4 with RNA interference induced cell motility, whereas knockdown of endogenous liprin alpha 1 suppressed cell motility. ING4 also suppressed cell motility that was enhanced by liprin alpha 1. However, ING4 did not further suppress cell motility when liprin alpha 1 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 alpha 1 to regulate cell migration and, with its known antiangiogenic function, may prevent invasion and metastasis.