Mori S, Chang J T, Andrechek E R, Matsumura N, Baba T, Yao G, Kim J W, Gatza M, Murphy S, Nevins J R
Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC 27708, USA.
Oncogene. 2009 Aug 6;28(31):2796-805. doi: 10.1038/onc.2009.139. Epub 2009 Jun 1.
The oncogenic phenotype is complex, resulting from the accumulation of multiple somatic mutations that lead to the deregulation of growth regulatory and cell fate controlling activities and pathways. The ability to dissect this complexity, so as to reveal discrete aspects of the biology underlying the oncogenic phenotype, is critical to understanding the various mechanisms of disease as well as to reveal opportunities for novel therapeutic strategies. Previous work has characterized the process of anchorage-independent growth of cancer cells in vitro as a key aspect of the tumor phenotype, particularly with respect to metastatic potential. Nevertheless, it remains a major challenge to translate these cell biology findings into the context of human tumors. We previously used DNA microarray assays to develop expression signatures, which have the capacity to identify subtle distinctions in biological states and can be used to connect in vitro and in vivo states. Here we describe the development of a signature of anchorage-independent growth, show that the signature exhibits characteristics of deregulated mitochondrial function and then demonstrate that the signature identifies human tumors with the potential for metastasis.
致癌表型是复杂的,它是由多个体细胞突变的积累导致的,这些突变会导致生长调节和细胞命运控制活动及途径的失调。剖析这种复杂性,以揭示致癌表型背后生物学的离散方面,对于理解疾病的各种机制以及揭示新治疗策略的机会至关重要。先前的工作已将癌细胞在体外的非锚定依赖性生长过程表征为肿瘤表型的一个关键方面,特别是在转移潜能方面。然而,将这些细胞生物学发现转化到人类肿瘤的背景下仍然是一项重大挑战。我们先前使用DNA微阵列分析来开发表达特征,这些特征有能力识别生物学状态中的细微差异,并可用于连接体外和体内状态。在这里,我们描述了一种非锚定依赖性生长特征的开发,表明该特征表现出线粒体功能失调的特征,然后证明该特征可识别具有转移潜能的人类肿瘤。