Selective amino acid restriction differentially affects the motility and directionality of DU145 and PC3 prostate cancer cells
Selective amino acid restriction differentially affects the motility and directionality of DU145 and PC3 prostate cancer cells
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DOI：
10.1002/jcp.21490
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发表时间：
2008-10-01
影响因子：
5.6
通讯作者：
Meadows, Gary G.
中科院分区：
文献类型：
--
作者：
Fu, Ya-Min;Yu, Zu-Xi;Meadows, Gary G.
我们以前发现，选择性限制氨基酸抑制两种雄激素非依赖性人前列腺癌细胞系DU 145和PC 3的侵袭。在这里，我们表明，在这两种细胞系中，酪氨酸（Tyr）和苯丙氨酸（Phe）、甲硫氨酸（Met）或谷氨酰胺（Gln）的限制调节G蛋白的活性，并影响两种肌动蛋白结合蛋白（cofilin和profilin）之间的平衡。在DU 145细胞中，选择性氨基酸限制差异性地降低G蛋白与GTP的结合。Tyr/Phe剥夺降低Rho-GTP和Rac 1-GTP的量。Met剥夺减少Ras-GTP和Rho-GTP的量，并且Gln剥夺减少Ras-GTP、3Rac-GTP和Cdc 42-GTP的量。这些氨基酸的限制增加了profilin、cofilin和cofilin-Ser的磷酸化的量（3）JAK 1表达的增加和PAK 1-Thr（423）和Ser（199/204）的磷酸化与LIMK 1-Thr（508）的磷酸化的增加一致。在PC 3细胞中，Tyr/Phe或Gln剥夺减少了Ras-GTP的量，并且所有检查的氨基酸限制减少了profilin的量。PAK 1、LIMK I和cofilin没有显著改变。这些数据表明，特定的氨基酸剥夺差异影响肌动蛋白动力学DU 145和PC 3。对Rho、Rac、PAK 1和LIMK I的调节可能改变DU 145细胞中cofilin和profilin之间的平衡。相反，在PC 3细胞中，profilin被抑制。这些作用调节方向性和运动性以抑制侵袭。
We previously found that selective restriction of amino acids inhibits invasion of two androgen-independent human prostate cancer cell lines, DU145 and PC3. Here we show that the restriction of tyrosine (Tyr) and phenylalanine (Phe), methionine (Met) or glutamine (Gln) modulates the activity of G proteins and affects the balance between two actin-binding proteins, cofilin and profilin, in these two cell lines. Selective amino acid restriction differentially reduces G protein binding to GTP in DU 145 cells. Tyr/Phe deprivation reduces the amount of Rho-GTP and Rac 1-GTP. Met deprivation reduces the amount of Ras-GTP and Rho-GTP, and GIn deprivation decreases Ras-GTP, 3 Rac-GTP, and Cdc42-GTP. Restriction of these amino acids increases the amount of profilin, cofilin and phosphorylation of cofilin-Ser(3) .Increased PAK 1 expression and phosphorylation of PAK 1-Thr(423), and Ser(199/204) are consistent with the increased phosphorylation of LIMK1-Thr(508). In PC3 cells, Tyr/Phe or GIn deprivation reduces the amount of Ras-GTP, and all of the examined amino acid restrictions reduce the amount of profilin. PAK 1, LIMK I and cofilin are not significantly altered. These data reveal that specific amino acid deprivation differentially affects actin dynamics in DU 145 and PC3. Modulation on Rho, Rac, PAK 1, and LIMK I likely alter the balance between cofilin and profilin in DU 145 cells. In contrast, profilin is inhibited in PC3 cells. These effects modulate directionality and motility to inhibit invasion.