Choline-releasing glycerophosphodiesterase EDI3 links the tumor metabolome to signaling network activities.
Choline-releasing glycerophosphodiesterase EDI3 links the tumor metabolome to signaling network activities.
复制标题
DOI：
10.4161/cc.22544
复制
发表时间：
2012-12-15
期刊：
影响因子：
--
通讯作者：
Hengstler JG
中科院分区：
文献类型：
--
作者：
Marchan R;Lesjak MS;Stewart JD;Winter R;Seeliger J;Hengstler JG
最近，EDI 3被鉴定为胆碱代谢的关键因子，其控制肿瘤细胞迁移并与子宫内膜癌的转移相关。EDI 3裂解甘油磷酸胆碱（GPC）以形成胆碱和甘油-3-磷酸（G3 P）。然后胆碱进一步代谢为磷脂酰胆碱（PtdC），这是膜中的主要脂质，也是膜介导的细胞信号传导的关键参与者。第二种产物G3 P是在信号传导中起核心作用的几种脂质的前体分子，例如溶血磷脂酸（LPA）、磷脂酸（PA）和二酰基甘油（DAG）。LPA通过与特异性LPA受体（包括膜结合G蛋白偶联受体和细胞内核受体PPARγ）结合来激活细胞内信号传导途径。相反，PA和DAG通过充当结合并激活几种信号蛋白的脂质锚来介导信号传导。例如，GTP酶和PKC分别与PA和DAG的结合增加了信号传导网络的激活，介导了诸如迁移、粘附、增殖或抗凋亡的过程-所有这些都与肿瘤发展相关。我们提出了一个概念，EDI 3直接产生信号分子或提供“膜锚”的下游信号因子。因此，EDI 3将胆碱代谢与信号传导活动联系起来，导致更恶性的表型。
Recently, EDI3 was identified as a key factor for choline metabolism that controls tumor cell migration and is associated with metastasis in endometrial carcinomas. EDI3 cleaves glycerophosphocholine (GPC) to form choline and glycerol-3-phosphate (G3P). Choline is then further metabolized to phosphatidylcholine (PtdC), the major lipid in membranes and a key player in membrane-mediated cell signaling. The second product, G3P, is a precursor molecule for several lipids with central roles in signaling, for example lysophosphatidic acid (LPA), phosphatidic acid (PA) and diacylglycerol (DAG). LPA activates intracellular signaling pathways by binding to specific LPA receptors, including membrane-bound G protein-coupled receptors and the intracellular nuclear receptor, PPARγ. Conversely, PA and DAG mediate signaling by acting as lipid anchors that bind and activate several signaling proteins. For example, binding of GTPases and PKC to PA and DAG, respectively, increases the activation of signaling networks, mediating processes such as migration, adhesion, proliferation or anti-apoptosis—all relevant for tumor development. We present a concept by which EDI3 either directly generates signaling molecules or provides “membrane anchors” for downstream signaling factors. As a result, EDI3 links choline metabolism to signaling activities resulting in a more malignant phenotype.
登录
查看更多内容
影响因子：
3.8
作者：
Moestue SA;Borgan E;Huuse EM;Lindholm EM;Sitter B;Børresen-Dale AL;Engebraaten O;Maelandsmo GM;Gribbestad IS
通讯作者：
Gribbestad IS
影响因子：
3.8
作者：
Cao MD;Giskeødegård GF;Bathen TF;Sitter B;Bofin A;Lønning PE;Lundgren S;Gribbestad IS
通讯作者：
Gribbestad IS
DOI：
10.1016/0925-4439(93)90124-j
发表时间：
1993-11-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
BELL, JD;COX, IJ;URENJAK, J
通讯作者：
URENJAK, J
影响因子：
56.9
作者：
Fang, YM;Vilella-Bach, M;Chen, J
通讯作者：
Chen, J
影响因子：
3.3
作者：
Chae, Young Chan;Kim, Jung Hwan;Ryu, Sung Ho
通讯作者：
Ryu, Sung Ho