Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling
Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling
复制标题
DOI：
10.1038/nature06835
复制
发表时间：
2008-04-03
期刊：
影响因子：
64.8
通讯作者：
Huelsken, Joerg
中科院分区：
文献类型：
--
作者：
Malanchi, Ilaria;Peinado, Hector;Huelsken, Joerg
组织特异性干细胞广泛的自我更新能力保证了上皮细胞的持续更新(1)。类似地，上皮性肿瘤的维持依赖于癌症干细胞（CSCs），它可以吸收干细胞的特性(2)。对于大多数肿瘤，这些CSCs的细胞起源和维持干细胞性所必需的调控途径尚未确定。在小鼠皮肤中，卵泡形态发生是由特异性表达CD34的鼓包干细胞驱动的。在这里，我们鉴定了早期表皮肿瘤的细胞群，其特征是表型和功能与正常皮肤干细胞相似。这个群体包含CSCs，这是唯一具有肿瘤起始特性的细胞。来源于这些csc的移植保存了原发肿瘤的等级组织。我们将β -连环蛋白信号传导(3)描述为维持CSC表型所必需的。β -连环蛋白基因的消融导致CSCs的丢失和肿瘤的完全消退。此外，我们提供的证据表明，增加β -连环蛋白信号参与恶性人类鳞状细胞癌。由于Wnt/ β -连环蛋白信号传导对于正常表皮稳态不是必需的，因此这种机制上的差异可以靶向消除CSCs(4)，从而根除鳞状细胞癌。
Continuous turnover of epithelia is ensured by the extensive self-renewal capacity of tissue- specific stem cells(1). Similarly, epithelial tumour maintenance relies on cancer stem cells ( CSCs), which co-opt stem cell properties(2). For most tumours, the cellular origin of these CSCs and regulatory pathways essential for sustaining stemness have not been identified. In murine skin, follicular morphogenesis is driven by bulge stem cells that specifically express CD34. Here we identify a population of cells in early epidermal tumours characterized by phenotypic and functional similarities to normal bulge skin stem cells. This population contains CSCs, which are the only cells with tumour initiation properties. Transplants derived from these CSCs preserve the hierarchical organization of the primary tumour. We describe beta-catenin signalling(3) as being essential in sustaining the CSC phenotype. Ablation of the beta-catenin gene results in the loss of CSCs and complete tumour regression. In addition, we provide evidence for the involvement of increased beta-catenin signalling in malignant human squamous cell carcinomas. Because Wnt/beta-catenin signalling is not essential for normal epidermal homeostasis, such a mechanistic difference may thus be targeted to eliminate CSCs(4) and consequently eradicate squamous cell carcinomas.