نقش SOX2 در توسعه و زیست شناسی سرطان
Abstract
1- Introduction
2- SOX2 in development
3- The role of SOX2 in embryonic and adult stem cells
4- The role of SOX2 in disease and cancer
5- Conclusions and future perspectives
References
Abstract
The transcription factor SOX2 is essential for embryonic development and plays a crucial role in maintaining the stemness of embryonic cells and various adult stem cell populations. On the other hand, dysregulation of SOX2 expression is associated with a multitude of cancer types and it has been shown that SOX2 positively affects cancer cell traits such as the capacity to proliferate, migrate, invade and metastasize. Moreover, there is growing evidence that SOX2 mediates resistance towards established cancer therapies and that it is expressed in cancer stem cells. These findings indicate that studying the role of SOX2 in the context of cancer progression could lead to the development of new therapeutic options. In this review, the current knowledge about the role of SOX2 in development, maintenance of stemness, cancer progression and the resistance towards cancer therapies is summarized.
Introduction
In 1990, a new transcription factor with a distinctive DNA-binding domain was described to be involved in testis determination. The gene encoding for this protein was found to be located on the sex-determining region of the Y chromosome and was therefore termed sexdetermining region Y (SRY) gene [1,2]. The Sry protein binds to specific DNA sequences with its high-mobility-group (HMG) domain. Since its discovery a new gene family has been established on the basis of sequence similarities to this HMG domain (Fig. 1). The so-called Sry-related HMG box (SOX) proteins contain an HMG domain with at least 50% sequence similarity to the HMG domain of Sry. Up to the present day, 20 different SOX genes have been found in the murine and human genome which in turn have been divided into eight subgroups based on sequence identity and similar functions [3,4]. In this review, we will focus on SOX2, a member of the SOXB1 subgroup. Among all SOX genes, SOX2 is probably the most recognized due to its role in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) [5]. The human SOX2 gene is situated on chromosome 3 at the position q26.3–27 and encodes for a protein of 317 amino acids [6]. The structural centerpiece of SOX2 is its HMG domain that is highly conserved among species. Apart from binding to specific DNA consensus sequences, this domain also contains a nuclear localization and a nuclear export signal. The function of the C-terminal transactivation domain is to recognize and bind the promoters of target genes and by doing so activating or repressing gene expression [7].