Protein interacting with C kinase 1 suppresses invasion and anchorage-independent growth of astrocytic tumor cells.
Protein interacting with C kinase 1 suppresses invasion and anchorage-independent growth of astrocytic tumor cells.
复制标题
DOI：
10.1091/mbc.e15-05-0270
复制
发表时间：
2015-12-15
影响因子：
3.3
通讯作者：
Hanley JG
中科院分区：
文献类型：
--
作者：
Cockbill LM;Murk K;Love S;Hanley JG
星形细胞瘤具有高度侵袭性，但其机制尚不清楚。PICK1在星形细胞瘤细胞系和临床病例中表达降低。外源性PICK1表达可降低肿瘤细胞系的侵袭能力和非贴壁依赖性生长。数据表明PICK1可能是治疗干预的一个靶点。
星形细胞瘤是原发性脑肿瘤最常见的形式。星形细胞瘤细胞浸润周围的中枢神经系统组织，使其在原发性肿瘤手术切除时能够逃避清除。肌动蛋白细胞骨架的动态变化对癌细胞侵袭至关重要，但星形细胞瘤细胞特别具有侵袭性表型的具体机制尚不清楚。与C激酶1相互作用的蛋白（PICK1）是一种含PDZ和BAR结构域的蛋白，它抑制肌动蛋白相关蛋白2/3（Arp2/3）依赖的肌动蛋白聚合，并参与调节许多细胞表面受体的运输。在此我们报道，与其他癌症相反，PICK1在Ⅳ级星形细胞瘤细胞系中以及在由低级别肿瘤进展而来的Ⅳ级肿瘤的临床病例中表达下调。在Ⅳ级星形细胞瘤细胞系U251中外源性表达PICK1可降低其非贴壁依赖性生长、二维迁移以及穿过三维基质侵袭的能力，这有力地表明PICK1低表达在星形细胞瘤发生中起重要作用。我们提出PICK1对星形细胞瘤的肿瘤浸润具有负调控作用，并且对PICK1的操作是治疗干预的一种有吸引力的可能性。
Astrocytic tumors are highly invasive, but the mechanisms are unclear. PICK1 has reduced expression in astrocytic tumor cell lines and clinical cases. Exogenous PICK1 expression reduces invasion and anchorage-independent growth of a tumor cell line. The data suggest that PICK1 may be a target for therapeutic intervention. Astrocytic tumors are the most common form of primary brain tumor. Astrocytic tumor cells infiltrate the surrounding CNS tissue, allowing them to evade removal upon surgical resection of the primary tumor. Dynamic changes to the actin cytoskeleton are crucial to cancer cell invasion, but the specific mechanisms that underlie the particularly invasive phenotype of astrocytic tumor cells are unclear. Protein interacting with C kinase 1 (PICK1) is a PDZ and BAR domain–containing protein that inhibits actin-related protein 2/3 (Arp2/3)-dependent actin polymerization and is involved in regulating the trafficking of a number of cell-surface receptors. Here we report that, in contrast to other cancers, PICK1 expression is down-regulated in grade IV astrocytic tumor cell lines and also in clinical cases of the disease in which grade IV tumors have progressed from lower-grade tumors. Exogenous expression of PICK1 in the grade IV astrocytic cell line U251 reduces their capacity for anchorage-independent growth, two-dimensional migration, and invasion through a three-dimensional matrix, strongly suggesting that low PICK1 expression plays an important role in astrocytic tumorigenesis. We propose that PICK1 negatively regulates neoplastic infiltration of astrocytic tumors and that manipulation of PICK1 is an attractive possibility for therapeutic intervention.