调控癌细胞骨架,抑制大肠癌转移
创作:Lexi 审核:Lexi 2020年09月14日
  • 体外实验中,4-对羟基苯乙酮(4-HAP)限制人结直肠癌细胞系HCT116粘附、侵袭和转移;
  • 在小鼠体内实验中,4-HAP可抑制脾脏注射的HCT116肿瘤发展和转移;
  • 4-HAP可增加HCT116细胞的皮质张力,但该过程不依赖非肌细胞肌球蛋白-2C(MYH14);
  • HCT116细胞具有大量肌动蛋白,但无应力纤维;
  • 4-HAP可激活癌细胞的MYH14、改变肌动蛋白组织,并抑制癌细胞转移的机械程序,从而阻止癌细胞转移。
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Lexi
癌细胞转移是绝大多数癌症死亡的原因。在转移过程中,细胞迁移到脉管系统、溢出、外渗并建立转移细胞群落。这种扩散模式需要癌细胞改变形状并绕过组织屏障。最新发表在PNAS的研究发现,通过改变癌细胞肌动蛋白组织形式,可抑制结肠癌细胞转移的机械程序,从而抑制癌细胞转移。
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PNAS [IF:9.412]

4-Hydroxyacetophenone modulates the actomyosin cytoskeleton to reduce metastasis

4-对羟基苯乙酮调控肌动球蛋白细胞骨架以减少肿瘤转移

10.1073/pnas.2014639117

2020-08-26, Article

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Abstract:收起
Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (MYH14) to alter actin organization, inhibiting the mechanical program of metastasis. We identify NM2C as a specific therapeutic target. Pharmacological control of myosin isoforms is a promising approach to address metastatic disease, one that may be readily combined with other therapeutic strategies.

First Authors:
Darren S Bryan,Melinda Stack

Correspondence Authors:
Ronald S Rock,Ralph R Weichselbaum

All Authors:
Darren S Bryan,Melinda Stack,Katarzyna Krysztofiak,Urszula Cichoń,Dustin G Thomas,Alexandra Surcel,Eric S Schiffhauer,Michael A Beckett,Nikolai N Khodarev,Lai Xue,Elizabeth C Poli,Alexander T Pearson,Mitchell C Posner,Douglas N Robinson,Ronald S Rock,Ralph R Weichselbaum

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Medical Xpress新闻网站

Small molecule treatment reduces colon cancer metastasis

2020-08-24

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