PLoS ONE：抑制癌基因RhoC降低乳腺癌干细胞转移

癌症干细胞是肿瘤组织内一类比较小的细胞类型，被认为可以刺激肿瘤生长和扩散。研究人员认为，传统的化疗和放射治疗往往无效的原因就是因为没有杀死癌症干细胞，因此未来治疗癌症的关键是开发那些能杀死这些细胞的药物。

这一最新研究发现涉及癌基因RhoC，RhoC已被证明可以促进多种癌症的转移。在乳腺癌发展过程中RhoC水平会增加，RhoC的高水平表达与病人的生存较差相关。

这项新的研究发表在PLoS ONE杂志上，阐述了一种新的获取癌症干细胞中的途径。针对特定的分子得到癌症干细胞为开发有潜力的癌症治疗方法铺平了道路。

消除癌症干细胞对治疗某些癌症是非常有必要的，但在这之前，我们必须能处理癌症干细胞侵袭等一系列生物学行为，密歇根大学的内科和流行病学教授、U-M综合癌症中心乳房肿瘤科学主任Sofia D. Merajver医学博士等人发现RhoC可以当做控制处理癌症干细胞的靶蛋白。

研究者用正常乳腺组织中细胞以及高转移性细胞株来开展研究，通过抑制或过度表达RhoC，他们发现RhoC的表达对两个细胞系的转移是必要的，RhoC的过表达可引起肿瘤转移。研究人员在小鼠体内研究中得到了类似的结果。

目前，研究团队正在积极来发一种新型的RhoC小分子药物抑制剂，并且已在实验室初步研究结果中显示出很大的研究前景。

编译自：Researchers find driver of breast cancer stem cell metastasis

doi:10.1371/journal.pone.0040979
PMC:
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RhoC Impacts the Metastatic Potential and Abundance of Breast Cancer Stem Cells

Devin T. Rosenthal1,2¤, Jie Zhang1, Liwei Bao1,et al.

Cancer stem cells (CSCs) have been shown to promote tumorigenesis of many tumor types, including breast, although their relevance to cancer metastasis remains unclear. While subpopulations of CSCs required for metastasis have been identified, to date there are no known molecular regulators of breast CSC (BCSC) metastasis. Here we identify RhoC GTPase as an important regulator of BCSC metastasis, and present evidence suggesting that RhoC also modulates the frequency of BCSCs within a population. Using an orthotopic xenograft model of spontaneous metastasis we discover that RhoC is both necessary and sufficient to promote SUM149 and MCF-10A BCSC metastasis–often independent from primary tumor formation–and can even induce metastasis of non-BCSCs within these cell lines. The relationship between RhoC and BCSCs persists in breast cancer patients, as expression of RhoC and the BCSC marker ALDH1 are highly correlated in clinical specimens. These results suggest new avenues to combating the deadliest cells driving the most lethal stage of breast cancer progression.