Lysyl oxidase propeptide inhibits prostate cancer cell growth by mechanisms that target FGF-2-cell binding and signaling.
Lysyl oxidase propeptide inhibits prostate cancer cell growth by mechanisms that target FGF-2-cell binding and signaling.
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DOI：
10.1038/onc.2009.203
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发表时间：
2009-09-24
期刊：
影响因子：
8
通讯作者：
Trackman, P. C.
中科院分区：
文献类型：
--
作者：
Palamakumbura, A. H.;Vora, S. R.;Nugent, M. A.;Kirsch, K. H.;Sonenshein, G. E.;Trackman, P. C.
前列腺癌细胞RAS信号增强和雄激素依赖性降低伴随着不良的临床结局。高自分泌的成纤维细胞生长因子-2信号促进前列腺癌细胞的生长和存活。赖氨酰氧化酶(LOX)的表达抑制RAS的转化活性。LOX被分泌为50 kDa的赖氨酰氧化酶原蛋白，然后经过胞外蛋白降解，形成~30 kDa的赖氨酰氧化酶和~18 kDa的前肽(LOX-PP)。我们先前已经证明LOX-PP抑制乳腺癌细胞转化和肿瘤形成，但LOX-PP的作用机制尚未完全阐明。在此，我们报道了LOX在前列腺癌细胞系中的表达降低，重组LOX-PP蛋白抑制了血清刺激的DNA合成以及DU 145和PC-3雄激素非依赖性细胞系的MEK/ERK和PI3K/AKT通路。在DU 145细胞中，用药理学的成纤维细胞生长因子受体抑制剂或中和抗FGFR1抗体处理可模拟LOX-PP抑制血清刺激的DNA合成。在DU145细胞中，LOX-PP可抑制成纤维细胞生长因子-2刺激的α合成、ERK1/2、AKT和FRS2的激活。LOX-PP降低了成纤维细胞生长因子-2与DU 145细胞的特异性结合，提示LOX-PP作用于受体上的成纤维细胞生长因子信号转导通路。有趣的是，PC-3细胞对成纤维细胞生长因子-2没有反应，这与以前的报道一致。结论：LOX-PP通过干扰FGFR(S)结合和信号转导抑制DU145细胞的增殖，对PC-3细胞有其他作用机制。
Enhanced RAS signaling and decreased androgen dependence of prostate cancer cells accompany poor clinical outcomes. Elevated autocrine FGF-2 signaling promotes prostate cancer cell growth and survival. Expression of lysyl oxidase (LOX) inhibits RAS transforming activity. LOX is secreted as 50 kDa pro-lysyl oxidase protein and then undergoes extracellular proteolytic processing to form ~30 kDa lysyl oxidase enzyme and ~18 kDa pro-peptide (LOX-PP). We have previously shown that LOX-PP inhibits breast cancer cell transformation and tumor formation, but mechanisms of action of LOX-PP have not been fully elucidated. Here we report that LOX expression is reduced in prostate cancer cell lines and that recombinant LOX-PP protein inhibits serum-stimulated DNA synthesis and MEK/ERK and PI3K/AKT pathways in DU 145 and PC-3 androgen-independent cell lines. In DU 145 cells, treatment with a pharmacologic FGF-receptor inhibitor or a neutralizing anti-FGFR1 antibody mimicked LOX-PP inhibition of serum-stimulated DNA synthesis. FGF-2-stimulated DNA synthesis, ERK1/2, AKT, and FRS2α activation were found all to be inhibited by LOX-PP in DU 145 cells. LOX-PP reduced specific binding of FGF-2 to DU 145 cells, suggesting that LOX-PP targets FGF signaling at the receptor. Interestingly, PC-3 cells did not respond to FGF-2, consistent with previous reports. We conclude that LOX-PP inhibits proliferation of DU 145 cells by interfering with FGFR(s) binding and signaling, and that LOX-PP has other mechanisms of action in PC-3 cells.
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影响因子：
4.2
作者：
Bansal, R;Magge, S;Winkler, S
通讯作者：
Winkler, S
影响因子：
6
作者：
Giri, D;Ozen, M;Ittmann, M
通讯作者：
Ittmann, M
影响因子：
5.8
作者：
Erlich, Shlomit;Tal-Or, Pazit;Pinkas-Kramarski, Ronit
通讯作者：
Pinkas-Kramarski, Ronit
DOI：
10.1089/153685902760173863
发表时间：
2002-06-01
期刊：
HYBRIDOMA AND HYBRIDOMICS
影响因子：
--
作者：
Blanckaert, VD;Venkateswaran, S;Schelling, ME
通讯作者：
Schelling, ME
影响因子：
4.8
作者：
HAMALAINEN, ER;KEMPPAINEN, R;KIVIRIKKO, KI
通讯作者：
KIVIRIKKO, KI