SOX2 gene – master regulator of numerous cellular processes

Milena Stevanović, Danijela Drakulić, Marija Švirtlih, Danijela Stanisavljević, Vladanka Vuković, Marija Mojsin, Andrijana Klajn


Summary. The SOX (Sry-related HMG box) proteins comprise a group of transcription factors that act as key regulators of diverse developmental and physiological processes, ranging from blastocyst and germ layer formation to differentiation into adult tissues and organs. SOX proteins influence survival and proliferation, as well as cell fate decisions and consecutive lineage progression. Accordingly, SOX proteins are involved in multiple events, from maintenance of stem cells pluripotency, to driving their terminal differentiation into specialized cell types. The SOX2 transcription factor is pivotal for early development and the maintenance of undifferentiated embryonic stem cells (ESCs). This transcription factor plays a critical role in directing the differentiation to neural progenitors and in maintaining the properties of neural progenitor stem cells. It is a crucial transcription factor capable of reprogramming differentiated cells and reversing the epigenetic configuration of differentiated cells back to a pluripotent embryonic state. SOX2 has been found to be an immunogenic antigen in several types of cancers, and its overexpression has been reported in several types of solid tumors. Accumulating evidence suggests that SOX2 acts as an oncogene and recent evidence points toward pro-proliferative, prosurvival and/or antidifferentiation roles of the SOX2 protein. Given the crucial role of SOX2 in cell proliferation and/or antidifferentiation and its ability to endow cells with stemness potential, studying the effects of modulation of its expression has additional significance. Accordingly, we manipulated the level of SOX2 gene expression and generated cell clones that stably overexpress SOX2. We have studied the effects of SOX2 overexpression and present some of our recent findings that have highlighted the important roles of SOX2 in the maintenance of pluripotency, proliferation, neural differentiation and in the regulation of the migration capacity of cells. This review also presents our findings related to the interaction and crosstalk between the SOX2 gene and the Wnt signaling pathway.

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