Role of the autotaxin-lysophosphatidate axis in cancer resistance to chemotherapy and radiotherapy.
Role of the autotaxin-lysophosphatidate axis in cancer resistance to chemotherapy and radiotherapy.
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自分泌运动因子-溶血磷脂酸轴在癌症对化疗和放疗的抵抗中的作用。
DOI：
10.1016/j.bbalip.2012.08.015
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Tigyi GJ
中科院分区：
文献类型：
--
作者：
Brindley DN;Lin FT;Tigyi GJ
自分泌运动因子在癌症中的高表达通常与增加的肿瘤进展、血管生成和转移相关。这主要是因为自分泌运动因子产生的脂质生长因子，溶血磷脂酸（LPA），刺激细胞分裂，存活和迁移。最近已经证明，LPA的这些信号传导作用也产生对化疗和辐射诱导的细胞死亡的抗性。这尤其是由于LPA 2受体的刺激，其消耗细胞的Siva-1（一种促凋亡信号蛋白），并通过TRIP-6介导的机制刺激促存活激酶途径。LPA信号传导还增加1-磷酸鞘氨醇（一种促存活脂质）的形成。同时，LPA减少神经酰胺的积累，神经酰胺用于放射治疗和许多化学治疗剂以刺激细胞凋亡。细胞外LPA的信号传导作用通过其被作为胞外酶的脂质磷酸磷酸酶（LPP）家族去磷酸化而终止。此外，脂质磷酸酶-1减弱LPA受体和受体酪氨酸激酶激活下游的信号传导。这使得许多癌细胞对各种生长因子的作用过敏，因为它们通常表达低LPP 1/3活性。增加我们对LPA用于刺激细胞存活的复杂信号通路的理解应该确定新的治疗靶点，可以利用这些靶点来提高化疗和放疗的疗效。这篇文章是题为溶血磷脂研究进展的特刊的一部分。
High expression of autotaxin in cancers is often associated with increased tumor progression, angiogenesis and metastasis. This is explained mainly since autotaxin produces the lipid growth factor, lysophosphatidate (LPA), which stimulates cell division, survival and migration. It has recently become evident that these signaling effects of LPA also produce resistance to chemotherapy and radiation-induced cell death. This results especially from the stimulation of LPA2 receptors, which depletes the cell of Siva-1, a pro-apoptotic signaling protein and stimulates prosurvival kinase pathways through a mechanism mediated via TRIP-6. LPA signaling also increases the formation of sphingosine 1-phosphate, a pro-survival lipid. At the same time, LPA decreases the accumulation of ceramides, which are used in radiation therapy and by many chemotherapeutic agents to stimulate apoptosis. The signaling actions of extracellular LPA are terminated by its dephosphorylation by a family of lipid phosphate phosphatases (LPP) that act as ecto-enzymes. In addition, lipid phosphate phoshatase-1 attenuates signaling downstream of the activation of both LPA receptors and receptor tyrosine kinases. This makes many cancer cells hypersensitive to the action of various growth factors since they often express low LPP1/3 activity. Increasing our understanding of the complicated signaling pathways that are used by LPA to stimulate cell survival should identify new therapeutic targets that can be exploited to increase the efficacy of chemo- and radio-therapy. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
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影响因子：
3.7
作者：
David M;Wannecq E;Descotes F;Jansen S;Deux B;Ribeiro J;Serre CM;Grès S;Bendriss-Vermare N;Bollen M;Saez S;Aoki J;Saulnier-Blache JS;Clézardin P;Peyruchaud O
通讯作者：
Peyruchaud O
影响因子：
2.7
作者：
Durgam, GG;Tsukahara, R;Miller, DD
通讯作者：
Miller, DD
DOI：
10.1124/jpet.108.141911
发表时间：
2008-12-01
影响因子：
3.5
作者：
Ferry, Gilles;Moulharat, Natacha;Boutin, Jean A.
通讯作者：
Boutin, Jean A.
影响因子：
5.7
作者：
Flanagan, James M.;Funes, Juan M.;Boshoff, Chris
通讯作者：
Boshoff, Chris
影响因子：
8
作者：
Chen, YH;Zheng, Y;Foster, DA
通讯作者：
Foster, DA