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Anchorage-independent cell growth signature identifies tumors with metastatic potential

Oncogene volume 28, pages 2796–2805 (2009)Cite this article

Abstract

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.

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Acknowledgements

We thank Drs J-T Chi, T Hallstrom, L Kong, R Rempel, J Freedman, M Gatza, Dr B Balakumaran, H Dressman, Y Yokota, S Akiyama, T Inoue, M Oshimura, M Araki, H Saya, Aburatani, A Niida, K Araki, Y Taya and Y Ito for helpful discussions; A Bild, T Kitamura, M Eilers and H Hanafusa for providing materials; L Jakoi for help with experiments; and T Henry and K Culler for assistance with the preparation of the article. This work was supported by a grant (5U54CA-112952-05) from the NIH/NCI to JRN. SM was a research fellow of the Uehara Memorial Foundation and is a visiting scholar of Riken Genome Science Center.

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Author notes

  1. S Mori

    Present address: 4Current address: Genomic Oncology Programme, Cancer Science Institute Singapore, National University of Singapore, Singapore 117456.,

Authors and Affiliations

  1. Duke Institute for Genome Sciences and Policy, Duke University Medical Center, NC, Durham, USA

    S Mori, J T Chang, E R Andrechek, N Matsumura, T Baba, G Yao, J W Kim, M Gatza, S Murphy & J R Nevins

  2. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, NC, Durham, USA

    N Matsumura, T Baba & S Murphy

  3. Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan

    N Matsumura & T Baba

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Correspondence to J R Nevins.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Mori, S., Chang, J., Andrechek, E. et al. Anchorage-independent cell growth signature identifies tumors with metastatic potential. Oncogene 28, 2796–2805 (2009). https://doi.org/10.1038/onc.2009.139

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