Different roles of SOX genes in promotion of malignant behavior of glioblastoma cells

The presence of 20 SOX genes in human genome was identified and they are divided into eight
\ndistinct groups designated from A to H. SOX genes encode proteins that display properties of both
\narchitectural components of chromatin and classical transcription factors. SOX transcription
\nfactors have crucial roles during development, including blastocyst formation, gastrulation, germ
\nlayer formation, maintaining the pluripotency of stem cells, cell proliferation, sex determination,
\nneurogenesis, gliogenesis, and pituitary development. In adult tissues, they are involved in
\nregulation of cell survival, regeneration and homeostasis. On the other hand, numerous SOX genes
\nare expressed in brain tumors and play crucial roles in their development and maintenance.
\nGlioblastoma (GBM), grade IV glioma tumor, is the most common, most aggressive, and deadliest
\nbrain tumor, with a median survival time of 15 months regardless of surgical resections, radio- and
\nchemotherapy. Its initiation, progression, relapse and resistance to treatments are associated with
\nglioma stem cells. GBMs contain different subsets of glioma stem cells characterized by high
\nproliferation rate, self-renewal capacity and ability to differentiate into different cell types and a
\nquiescent state of these cells protect them against chemotherapy and radiotherapy. Almost all SOX
\ngenes are expressed in GBM and play roles in induction, progression and maintenance of
\nmalignant phenotype of GBM, acting as oncogenes, tumor suppressors, or both, depending on the
\ncellular context. They influence stemness, self-renewal, proliferation, viability, migration,
\ninvasion and sphere-forming capacity of glioma stem cells. Furthermore, SOX transcription factors
\ncontribute to the malignant phenotype of GBM by affecting proliferation, differentiation, viability,
\nmigration, invasion and apoptosis of GBM cells. SOX genes which function as oncogenes are
\nusually associated with a poor prognosis and shorter survival. Also, roles of the SOX2 and SOX9
\ngenes in the chemo- and radioresistance of this type of tumor are revealed.
\nOverall, understanding the molecular mechanisms underlying the GBM is crucial for the discovery
\nof more efficient therapeutic approaches for this type of tumor and many SOX genes have been
\nrecognized as promising candidates in the examination of new therapeutic targets.