Inhibition of prostate cancer proliferation by interference with SONICHEDGEHOG-GLI1 signaling
Inhibition of prostate cancer proliferation by interference with SONICHEDGEHOG-GLI1 signaling
复制标题
DOI：
10.1073/pnas.0404956101
复制
发表时间：
2004-08-24
影响因子：
11.1
通讯作者：
Altaba, ARI
中科院分区：
文献类型：
--
作者：
Sanchez, P;Hern치ndez, AM;Altaba, ARI
前列腺癌是男性中最常见的实体瘤，它与所有癌症一样具有升高的非稳态细胞增殖的特征。在这里，我们已经测试了假设，即声音刺猬（SHH）-GLI信号通路是牵连在前列腺癌。我们报道了SHH-GLI通路组分在成人前列腺癌中的表达，与正常前列腺上皮相比，肿瘤中SHH-GLI通路组分的表达水平通常较高。用环巴胺或抗SHH抗体阻断该途径可抑制GLI 1（+）/PSA（+）原发性前列腺肿瘤培养物的增殖。然而，SHH可以增强肿瘤细胞增殖，这表明自分泌信号通常可以维持肿瘤生长。此外，在三种转移性前列腺癌细胞系中，使用环巴胺或通过GLI 1 RNA干扰阻断通路导致细胞增殖抑制，表明细胞自主通路在不同水平上活化，并显示GLI 1在人类细胞中的重要作用。我们的数据表明前列腺癌对SHH-GLI功能的依赖性，并提出了一种新的治疗方法。
Prostate cancer is the most common solid tumor in men, and it shares with all cancers the hallmark of elevated, nonhomeostatic cell proliferation. Here we have tested the hypothesis that the SONIC HEDGEHOG (SHH)-GLI signaling pathway is implicated in prostate cancer. We report expression of SHH-GLI pathway components in adult human prostate cancer, often with enhanced levels in tumors versus normal prostatic epithelia. Blocking the pathway with cyclopamine or anti-SHH antibodies inhibits the proliferation of GLI1(+)/PSA(+) primary prostate tumor cultures. Inversely, SHH can potentiate tumor cell proliferation, suggesting that autocrine signaling may often sustain tumor growth. In addition, pathway blockade in three metastatic prostate cancer cell lines with cyclopamine or through GLI1 RNA interference leads to inhibition of cell proliferation, suggesting cell-autonomous pathway activation at different levels and showing an essential role for GLI1 in human cells. Our data demonstrate the dependence of prostate cancer on SHH-GLI function and suggest a novel therapeutic approach.