The Role of SOX-2 in Melanoma

SOX2 is a key regulatory gene that encodes a transcription factor important for embryonic stem cell pluripotency. While the molecular function that SOX2 plays in tumorigenesis remains to be determined, recent evidence points toward pro-proliferative, pro-survival and anti-differentiation roles. This work focuses on delineation of the functional roles of SOX2, its regulation mechanisms, and the implications of these changes on the acquisition of malignant phenotype of melanoma.

We have previously shown that SOX2 facilitates melanoma cell proliferation. By overexpressing SOX2 in several melanoma cell lines, we show that it also enhances melanoma cell migration. Further, we show that SOX2 expression is controlled by the MAPK pathway, as vemurafenib (a highly selective inhibitor of BRAF^V600E) decreases SOX2 protein expression. This is particularly important, as BRAF-mutant melanoma exhibits constitutive activation of the MAPK pathway and worse prognosis. In addition, we show that SOX2 is controlled post transcriptionally by the microRNA miR-607.

Collectively, our findings support a role for SOX2 in facilitating the aggressiveness of melanoma cells, which may contribute to the poor prognosis of BRAF-mutant patients. This information may be important in understanding mechanism of resistance to vemurafenib, which will be studied in future studies.