Phenotype switching in melanoma progression

JL Simmons, CJ Pierce, F Al-Ejeh and GM Boyle

QIMR Berghofer Medical Research Institute

Metastatic melanoma is an aggressive disease associated with poor survival, owing to a high level of therapeutic resistance. Phenotypic plasticity is an occurrence whereby tumour populations switch between proliferative and invasive states, also termed phenotype switching. It has been suggested that the aggressive nature and inherent chemotherapeutic resistance of metastatic melanoma is a result of this plasticity. Recent studies have shown mutually exclusive expression of the transcription factors MITF and BRN2 in metastatic melanoma tumours. Cells within proliferative regions of a tumour display high expression of MITF while invasive regions and disseminated tumour cells have increased expression of BRN2. This has lead to the suggestion that MITF and/or BRN2 may be contributing to phenotype switching in metastatic melanoma. Utilising both in vitro and in vivo methods we have investigated the relative contribution of these two transcription factors towards phenotype switching leading to melanoma metastasis.