Understanding the Role of BRN2 in Melanoma (Medicine)

The initiation of cancer requires both the activation of oncogenes and the loss of tumor suppressor activity. The major oncogenes that drive melanoma, an aggressive skin cancer, are well known and mutations that affect the activity of tumor suppressors such as PTEN have been characterized. But less is known about whether and how the levels of tumor suppressor affect total tumor suppressor activity in this cancer.

A study jointly led by Ludwig Oxford’s Colin Goding and Lionel Larue of the Institut Curie, in France, identified BRN2 as a tumor suppressor that regulates PTEN levels. The researchers report in Nature Communications that BRN2 is a key transcription factor that lies downstream of three melanoma-associated signaling pathways to control gene expression. A role for BRN2 in melanoma migration and invasiveness had previously been established through in vitro and xenograft experiments, but this is the first time that the function of BRN2 in melanoma initiation and proliferation has been demonstrated in an animal model engineered to develop melanoma.

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 melanoma cells in tumors, the study reinforces the importance of this factor in the cancer.

Reference: Hamm, M., Sohier, P., Petit, V. et al. BRN2 is a non-canonical melanoma tumor-suppressor. Nat Commun 12, 3707 (2021). https://doi.org/10.1038/s41467-021-23973-5

Provided by Ludwig Cancer Research

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