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FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and embryonic signalling pathways in cancer

Oncogene volume 34, pages 4421–4428 (2015)Cite this article

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Abstract

Tumour heterogeneity is a major factor undermining the success of therapies targeting metastatic cancer. Two major theories are thought to explain the phenomenon of heterogeneity in cancer—clonal evolution and cell plasticity. In this review, we examine a growing body of work implicating the transcription factor FOS-related antigen 1 (FRA-1) as a central node in tumour cell plasticity networks, and discuss mechanisms regulating its activity in cancer cells. We also discuss evidence from the FRA-1 perspective supporting the notion that clonal selection and cell plasticity represent two sides of the same coin. We propose that FRA-1-overexpressing clones featuring high plasticity undergo positive selection during consecutive stages of multistep tumour progression. This model underscores a potential mechanism through which tumour cells retaining elevated levels of plasticity acquire a selective advantage over other clonal populations within a tumour.

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Acknowledgements

We apologize to the colleagues whose relevant work we were unable to cite owing to space limitations. This work was supported by project grants from the National Health and Medical Research Council of Australia (to ASD), and Cancer Research UK (CRUK) and Association for International Cancer Research (AICR) (to ET).

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  1. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    A S Dhillon

  2. Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK

    E Tulchinsky

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Dhillon, A., Tulchinsky, E. FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and embryonic signalling pathways in cancer. Oncogene 34, 4421–4428 (2015). https://doi.org/10.1038/onc.2014.374

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  • DOI: https://doi.org/10.1038/onc.2014.374

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