Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells
Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells
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DOI：
10.1124/mol.107.040105
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发表时间：
2008-09-01
影响因子：
3.6
通讯作者：
Meier, Kathryn E.
中科院分区：
文献类型：
--
作者：
Knoepp, Stewart M.;Chahal, Manpreet S.;Meier, Kathryn E.
磷脂酰胆碱-使用磷脂酶D（PLD）同种型PLD 2在哺乳动物细胞中广泛表达，并且响应于多种促有丝分裂激动剂而被激活。在这项研究中，活性和无活性的血凝素标记的人PLD 2（HA-PLD 2）的构建体中稳定表达的EL 4细胞系缺乏可检测的内源性PLD 1或PLD 2。该研究的总体目标是检查PLD 2在细胞信号转导和细胞表型中的作用。HA-PLD 2赋予PLD活性，其被佛波酯、离子霉素和冈田酸激活。在用活性PLD 2转染的细胞中，增殖和Erk活化未改变;在表达无活性PLD 2的细胞中，增殖速率降低。在表达活性PLD 2的细胞中，粘着斑激酶（FAK）的基础酪氨酸磷酸化增加，Akt的磷酸化也增加;无活性PLD 2没有影响。活性PLD 2的表达与细胞在组织培养塑料上的扩展和伸长增加相关，而非活性PLD 2抑制细胞扩展。无活性的PLD 2还抑制细胞粘附、迁移和血清诱导的侵袭。表达活性PLD 2的细胞在同基因小鼠中形成转移，与亲本细胞一样;表达非活性PLD 2的细胞比亲本细胞形成更少的转移。总之，在EL 4淋巴瘤细胞中，活性PLD 2增强FAK磷酸化、Akt活化和细胞侵袭，而非活性PLD 2对粘附、迁移、侵袭和肿瘤形成发挥抑制作用。总体而言，活性PLD 2的表达增强有利于淋巴瘤细胞转移的过程，而非活性PLD 2的表达抑制转移。
The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectable endogenous PLD1 or PLD2. The overall goal of the study was to examine the roles of PLD2 in cellular signal transduction and cell phenotype. HA-PLD2 confers PLD activity that is activated by phorbol ester, ionomycin, and okadaic acid. Proliferation and Erk activation are unchanged in cells transfected with active PLD2; proliferation rate is decreased in cells expressing inactive PLD2. Basal tyrosine phosphorylation of focal adhesion kinase (FAK) is increased in cells expressing active PLD2, as is phosphorylation of Akt; inactive PLD2 has no effect. Expression of active PLD2 is associated with increased spreading and elongation of cells on tissue culture plastic, whereas inactive PLD2 inhibits cell spreading. Inactive PLD2 also inhibits cell adhesion, migration, and serum-induced invasion. Cells expressing active PLD2 form metastases in syngeneic mice, as do the parental cells; cells expressing inactive PLD2 form fewer metastases than parental cells. In summary, active PLD2 enhances FAK phosphorylation, Akt activation, and cell invasion in EL4 lymphoma cells, whereas inactive PLD2 exerts inhibitory effects on adhesion, migration, invasion, and tumor formation. Overall, expression of active PLD2 enhances processes favorable to lymphoma cell metastasis, whereas expression of inactive PLD2 inhibits metastasis.