Abstract
Transcriptional and epigenetic embryonic programs can be reactivated in cancer cells. As result, a specific subset of undifferentiated cells with stem-cells properties emerges and drives tumorigenesis. Recent findings have shown that ectoderm- and endoderm-derived tissues continue expressing stem-cells related transcription factors of the SOX-family of proteins such as SOX2 and SOX9 which have been implicated in the presence of cancer stem-like cells (CSCs) in tumors. Currently, there is enough evidence suggesting an oncogenic role for SOX9 in different types of human cancers. This review provides a summary of the current knowledge about the involvement of SOX9 in development and progression of cancer. Understanding the functional roles of SOX9 and clinical relevance is crucial for developing novel treatments targeting CSCs in cancer.
Highlights
There has been a growing interest in the study of mechanisms leading to the expression of genes involved in developmental and cell differentiation, since they are related to the presence of a special type of tumor cells with a stemness phenotype dubbed as cancer stem-like cells (CSCs)
SOX family of proteins comprise a group of transcriptional regulators containing a highly conserved high mobility group (HMG) domain that was first discovered in Sex-determining region Y (SRY) protein, a transcription factor involved in mammalian male sex determination [11]
SOX9 was transcriptionally activated following H. pylori infection in Gastric cancer (GC) cell and its silencing resulted in an increase of phospho-histone H3- (p-H3-) proliferative cells and spheres formation ability promoted by bacteria. βcatenin-silenced cells presented a marked reduction in pH3-positive cells when infected with both strains [26]
Summary
There has been a growing interest in the study of mechanisms leading to the expression of genes involved in developmental and cell differentiation, since they are related to the presence of a special type of tumor cells with a stemness phenotype dubbed as cancer stem-like cells (CSCs). Stem cells regulatory proteins are being recognized as potential oncogenes because of their ability to regulate CSCs phenotype and maintenance in tumors of diverse types of cancer. Sex-determining region Y (SRY)-box 9 protein (SOX9) is a member of the SOX family of transcription factors (TFs) which are developmental regulators that possess high mobility group (HMG) box DNA binding and transactivation domains [3]. It participates in a variety of functions, such as lineage restriction and terminal differentiation, through precise temporal and spatial expression patterns that differ between particular cell types and tissues [4]. In this review we aim to condense the knowledge about the involvement of SOX9 in the initiation and progression of different types of cancer and to highlight its potential as a clinical biomarker
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