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原文来自Oncogene , (17 January 2011) | doi:10.1038/onc.2010.591，由干细胞之家成员jiandong2001翻译。- `' ?! ]- [# d$ X# a- k
标题：Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion5 A3 }! m A, L/ W0 T) }
译文:Kruppel样因子4（KLF4）在超过70%的乳腺癌患者中高表达，并且具有癌基因的作用。然而，KLF4通过何种机制增强乳腺癌的致瘤性仍不清楚。本文中，作者发现KLF4在富含肿瘤干细胞的小鼠原发性乳腺肿瘤及乳腺癌细胞系中高表达。通过分析干细胞表面标志物如醛脱氢酶1、侧群细胞及体外成瘤能力等可证实，敲除乳腺癌细胞（MCF-7 及 MDA-MB-231）中的KLF4可减少肿瘤中干细胞/祖细胞的比例。与此一致的是，KLF4过渡表达可使肿瘤干细胞的比例增高。敲除KLF4后同样也抑制了 MCF-7 及 MDA-MB-231细胞的迁移及侵袭性。此外，敲除KLF4后还可减少肿瘤细胞体外集落形成能力，并抑制其在免疫缺陷小鼠体内的成瘤能力，这些均支持了KLF4在乳腺癌发生过程中的促瘤作用。进一步对该机制的研究显示，KLF4介导的细胞迁移与侵袭需借助Notch信号通路，维持肿瘤干细胞则不需要该通路。总之，本文提供了KLF4 在促进乳腺肿瘤发生中的潜在促瘤作用的证据，这一作用可能通过保持干细胞样特征及促进细胞迁移与侵袭实现。因此，靶向作用于KLF4有望提供一个抑制乳腺癌发生的有效治疗途径。# K" B; m% y! p7 P
原文：Kruppel-like factor 4 (KLF4) is highly expressed in more than 70% of breast cancers and functions as an oncogene. However, an exact mechanism by which KLF4 enhances tumorigenesis of breast cancer remains unknown. In this study, we show that KLF4 was highly expressed in cancer stem cell (CSC)-enriched populations in mouse primary mammary tumor and breast cancer cell lines. Knockdown of KLF4 in breast cancer cells (MCF-7 and MDA-MB-231) decreased the proportion of stem/progenitor cells as demonstrated by expression of stem cell surface markers such as aldehyde dehydrogenase 1, side population and by in vitro mammosphere assay. Consistently KLF4 overexpression led to an increase of the cancer stem cell population. KLF4 knockdown also suppressed cell migration and invasion in MCF-7 and MDA-MB-231 cells. Furthermore, knockdown of KLF4 reduced colony formation in vitro and inhibited tumorigenesis in immunocompromised non-obese diabetic/severe combined immunodeficiency mice, supporting an oncogenic role for KLF4 in breast cancer development. Further mechanistic studies revealed that the Notch signaling pathway was required for KLF4-mediated cell migration and invasion, but not for CSC maintenance. Taken together, our study provides evidence that KLF4 has a potent oncogenic role in mammary tumorigenesis likely by maintaining stem cell–like features and by promoting cell migration and invasion. Thus, targeting KLF4 may provide an effective therapeutic approach to suppress tumorigenicity in breast cancer.
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发表于 2011-1-22 10:22
