The Role of Sox Transcription Factors in Brain Tumourigenesis

Ferletta, Maria

doi:10.5772/23616

Cited by 3 publications

(5 citation statements)

References 119 publications

(214 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glioma stemness programs have been characterized over the last years suggesting important regulatory roles for different members of the HOX [ 20 , 56 ] and SOX [ 20 – 22 , 57 ] gene families. Roles of SOX genes in development and pathology have been reviewed in [ 58 ].…”

Section: Resultsmentioning

confidence: 99%

Comparative analysis of histologically classified oligodendrogliomas reveals characteristic molecular differences between subgroups

2018

View full text Add to dashboard Cite

BackgroundMolecular data of histologically classified oligodendrogliomas are available offering the possibility to stratify these human brain tumors into clinically relevant molecular subtypes.MethodsGene copy number, mutation, and expression data of 193 histologically classified oligodendrogliomas from The Cancer Genome Atlas (TCGA) were analyzed by well-established computational approaches (unsupervised clustering, statistical testing, network inference).ResultsWe applied hierarchical clustering to tumor gene copy number profiles and revealed three molecular subgroups within histologically classified oligodendrogliomas. We further screened these subgroups for molecular glioma markers (1p/19q co-deletion, IDH mutation, gain of chromosome 7 and loss of chromosome 10) and found that our subgroups largely resemble known molecular glioma subtypes. We excluded glioblastoma-like tumors (7a10d subgroup) and derived a gene expression signature distinguishing histologically classified oligodendrogliomas with concurrent 1p/19q co-deletion and IDH mutation (1p/19q subgroup) from those with predominant IDH mutation alone (IDHme subgroup). Interestingly, many signature genes were part of signaling pathways involved in the regulation of cell proliferation, differentiation, migration, and cell-cell contacts. We further learned a gene regulatory network associated with the gene expression signature revealing novel putative major regulators with functions in cytoskeleton remodeling (e.g. APBB1IP, VAV1, ARPC1B), apoptosis (CCNL2, CREB3L1), and neural development (e.g. MYTIL, SCRT1, MEF2C) potentially contributing to the manifestation of differences between both subgroups. Moreover, we revealed characteristic expression differences of several HOX and SOX transcription factors suggesting the activity of different glioma stemness programs in both subgroups.ConclusionsWe show that gene copy number profiles alone are sufficient to derive molecular subgroups of histologically classified oligodendrogliomas that are well-embedded into general glioma classification schemes. Moreover, our revealed novel putative major regulators and characteristic stemness signatures indicate that different developmental programs might be active in these subgroups, providing a basis for future studies.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4251-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Comparative analysis of histologically classified oligodendrogliomas reveals characteristic molecular differences between subgroups

2018

View full text Add to dashboard Cite

show abstract

“…12,13 There were many studies conducted to prove that SOX9 and the other members of SOX E (SOX8 and SOX10) contributed in CNS development. [8][9][10][11] Similarly like other SOX family members, the function of SOX9 is initiatiated when collaborate with other SOX in neurogenesis. The supplementary function of SOX9 with SOX10 may sustain the multipotency of neural crest stem cells of SOX and CNS tumours and commanding differentiating cells to non-neuronal fates.…”

Section: Discussionmentioning

confidence: 99%

“…7 Many studies have proven that SOX9 and the other members of SOX E (SOX8 and SOX10) contributed to CNS development. [8][9][10][11] SOX9 which is a member of the SOX E family has been shown to play a…”

mentioning

confidence: 99%

Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

Nb¹,

Wr²,

Mn³

et al. 2020

imjm

View full text Add to dashboard Cite

Introduction: SOX9, a members of SOX family, plays a significant roles in developmental processes during embryogenesis, including brain tissue. Few studies have shown that SOX9 has been involved in tumourigenesis of several types of cancer including brain tumour. However, such studies are still lacking in the Malaysian population. The aim of this study was to determine SOX9 expression level in several types of brain tumours in East Coast Malaysia. Materials and Methods: Five formalin-fixed pariffin-embedded brain tumour samples of Malay descendants were sectioned by using microtome. RNA extraction was performed with slight modification by adding Trizol during tissue lysis. The RNA was converted to cDNA using reverse transcription technique before SOX9 expression was detected using RT q-PCR assay in brain tumours normalized to non-neoplastic brain tissues. Results: Overall results displayed that SOX9 gene in all samples were up-regulated. SOX9 overexpression was found in both high and low grade glioma (anaplastic and pilocytic astrocytoma respectively). This is consistence with both low grade (benign) and atypical meningioma. Secondary brain tumour also showed up-regulation when compared to normal brain tissue. Conclusion: Up-regulation in SOX9 expression in selected brain tumours in Malay patients revealed its significant roles in brain tumourigenesis. Functional studies should be carried out to observe the SOX9 functions and mechanism whether they should reflect their diverse roles in Malaysia population.

show abstract

“…Recent data suggest that initiation and progression of brain tumors are driven by cancer stem‐like cells and several studies have shown that Sox2 is important for keeping normal neural stem cells in a proliferating and immature state . Sox2 is widely expressed in glioblastoma as well as in several glioma cell lines, although the major proportion of cell lines established in serum‐containing medium are Sox2 negative, which is not the case when established in defined stem cell medium …”

Section: Discussionmentioning

confidence: 99%

“…While a few reports suggest that Sox21 can promote differentiation of neural stem cells by counteracting the activity of Sox2, there are surprisingly few reports about the role of the Sox2/Sox21 axis during brain tumor development. Mallana et al .…”

Section: Discussionmentioning

confidence: 99%

Sox21 inhibits glioma progressionin vivoby forming complexes with Sox2 and stimulating aberrant differentiation

et al. 2013

Self Cite

View full text Add to dashboard Cite

Sox2 is a transcription factor in neural stem cells and keeps the cells immature and proliferative. Sox2 is expressed in primary human glioma such as glioblastoma multiforme (GBM), primary glioma cells and glioma cell lines and is implicated in signaling pathways in glioma connected to malignancy. Sox21, the counteracting partner of Sox2, has the same expression pattern as Sox2 in glioma but in general induces opposite effects. In this study, Sox21 was overexpressed by using a tetracycline-regulated expression system (tet-on) in glioma cells. The glioma cells were injected subcutaneously into immunodeficient mice. The control tumors were highly proliferative, contained microvascular proliferation and large necrotic areas typical of human GBM. Induction of Sox21 in the tumor cells resulted in a significant smaller tumor size, and the effect correlated with the onset of treatment, where earlier treatment gave smaller tumors. Mice injected with glioma cells orthotopically into the brain survived significantly longer when Sox21 expression was induced. Tumors originating from glioma cells with an induced expression of Sox21 exhibited an increased formation of Sox2:Sox21 complexes and an upregulation of S100b, CNPase and Tuj1. Sox21 appears to decrease the stem-like cell properties of the tumor cells and initiate aberrant differentiation of glioma cells in vivo. Taken together our results indicate that Sox21 can function as a tumor suppressor during gliomagenesis mediated by a shift in the balance between Sox2 and Sox21. The wide distribution of Sox2 and Sox21 in GBM makes the Sox2/ Sox21 axis a very interesting target for novel therapy of gliomas.

show abstract

The Role of Sox Transcription Factors in Brain Tumourigenesis

Cited by 3 publications

References 119 publications

Comparative analysis of histologically classified oligodendrogliomas reveals characteristic molecular differences between subgroups

Comparative analysis of histologically classified oligodendrogliomas reveals characteristic molecular differences between subgroups

Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

Sox21 inhibits glioma progressionin vivoby forming complexes with Sox2 and stimulating aberrant differentiation

Contact Info

Product

Resources

About