FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and embryonic signalling pathways in cancer.
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.
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
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AS
Dhillon
Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
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Tulchinsky
D000818:Animals; D060965:Clonal Evolution; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D009857:Oncogenes; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D016212:Transforming Growth Factor beta; D000099169:Fos-Related Antigen 1