Sci Rep:Hsp抑制剂对纤连蛋白转运的异常调节能够抑制前列腺癌细胞的入侵

2018-02-11 AlexYang MedSci原创

分子伴侣Hsp90在前列腺癌(PCa)中过表达并且与多种癌基因蛋白的折叠、稳定化和成熟相关,这些均与PCa的恶化相关。与第一代Hsp90抑制剂相比,比如17-allylamino-demeth oxygeldanamycin(17-AGG)在临床治疗中效果较差,而第二代抑制剂AUY922具有更好的溶解性和治疗效果。最近,有研究人员对病人来源的PCa外植体的转录组和蛋白组分析鉴定了细胞骨架组织在AU

分子伴侣Hsp90在前列腺癌(PCa)中过表达并且与多种癌基因蛋白的折叠、稳定化和成熟相关,这些均与PCa的恶化相关。与第一代Hsp90抑制剂相比,比如17-allylamino-demeth oxygeldanamycin(17-AGG)在临床治疗中效果较差,而第二代抑制剂AUY922具有更好的溶解性和治疗效果。

最近,有研究人员对病人来源的PCa外植体的转录组和蛋白组分析鉴定了细胞骨架组织在AUY922处理下高度富集。在PCa细胞系中的分析阐释了与安慰剂或者17-AAG相比,AUY922能够引起细胞形态的显著的改变、并且抑制了细胞的移动和入侵,并且伴随了关键细胞外基质蛋白的异常调节,比如纤连蛋白(FN1)。有趣的是,虽然FN1的表达在AUY922处理下增加,FN1分泌显著降低。上述现象也导致了FN1蛋白在晚期核内体的胞质积累,表明了AUY922干扰了泡囊分泌通路。另外,利用siRNA敲除引起的FN1蛋白的缺失能够显著的减少PCa细胞的入侵能力,与AUY922引起的表型相似。

最后,研究人员指出,这些结果强调了除了对细胞有丝分裂和生存具有影响外,AUY922功能的一个新的机制。进一步的是,研究人员还鉴定了细胞外传输基质可以作为治疗恶性PCa的一种潜在的治疗靶标。

原始出处:

Heather K. Armstrong, Joanna L. Gillis, Ian R. D. Johnson et al. Dysregulated fibronectin trafficking by Hsp90 inhibition restricts prostate cancer cell invasion. Sci Rep. 1 Feb 2018.

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    2018-09-03 yzh409
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    2018-09-30 jklm09
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    2018-02-16 周周人

    学习.

    0

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    2018-02-16 sunfeifeiyang

    0

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    2018-02-13 yxch36
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