Initiation of cancer requires both the activation of oncogenes and the loss of tumour suppressor activity. In melanoma, an aggressive type of skin cancer, the major oncogenes are well known and mutations that affect the activity of tumour suppressors such as PTEN have been characterised. However, less is known about whether and how the levels of tumour suppressor protein are altered in melanoma to impact total tumour suppressor activity.
A study jointly led by Professor Colin Goding (Ludwig Oxford) and Dr Lionel Larue (Institut Curie, France) identified BRN2 as a tumour suppressor that regulates PTEN levels. BRN2 is a key transcription factor that lies downstream of three melanoma-associated signalling pathways to control gene expression. A role for BRN2 in melanoma migration and invasiveness had previously been established from in vitro and xenograft experiments but this is the first time that the function of BRN2 in melanoma initiation and proliferation has been found in vivo.
The authors also uncovered a link between BRN2 loss or low levels and worse prognosis for patients with melanoma. Together with previous collaborative observations from the Goding and Larue groups showing BRN2 is linked to a high mutation burden and marks a distinct subpopulation of melanomas cells in tumours, this study reinforces the importance of this factor in melanoma.