Sox2: regulation of expression and contribution to brain tumors

Mansouri, Sheila; Nejad, Romina; Karabork, Merve; Ekinci, Can; Solaroğlu, İhsan; Aldape, Kenneth; Zadeh, Gelareh

doi:10.2217/cns-2016-0001

Cited by 32 publications

(23 citation statements)

References 140 publications

(181 reference statements)

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“…Strong expression of nodules for alpha‐internexin, an intermediate neurofilament expressed in neuroblasts has also been previously shown in MVNT , but more variable expression of nestin in line with our observations. We also noted intense expression of stem cell markers SOX2 and CD34, which has been consistently reported in CNS tumors, LEATS and FCD .…”

Section: Discussionsupporting

confidence: 80%

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

et al. 2017

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Multinodular and vacuolating neuronal tumor (MVNT) is a new pattern of neuronal tumour included in the recently revised WHO 2016 classification of tumors of the CNS. There are 15 reports in the literature to date. They are typically associated with late onset epilepsy and a neoplastic vs. malformative biology has been questioned. We present a series of ten cases and compare their pathological and genetic features to better characterized epilepsy‐associated malformations including focal cortical dysplasia type II (FCDII) and low‐grade epilepsy‐associated tumors (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi‐gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre‐operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro‐glial cell type showing aberrant maturation.

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Section: Discussionsupporting

confidence: 80%

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

et al. 2017

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“…In patients with breast or ovarian cancer for example, SOX2 induction is already observed at early disease stages and further associates with disease progression, metastasis, and relapse [40,43,45,46]. In glioblastoma as another example, elevated SOX2 expression associates with increased cell motility and tumor spreading and is also detected amongst circulating CSC islets [49][50][51]. Further involving SOX2 in cancer stemness, elevated SOX2 expression associates with chemotherapyresistance effects [52], induces stemness and endothelial-tomesenchymal-transition gene signatures [17], and promotes clonogenicity and in vivo tumorigenicity in respective model systems [43,52].…”

Section: Functional Roles Of Sox2mentioning

confidence: 99%

SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond

2019

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Research of the past view years expanded our understanding of the various physiological functions the cell-fate determining transcription factor SOX2 exerts in ontogenesis, reprogramming, and cancer. However, while scientific reports featuring novel and exciting aspects of SOX2-driven biology are published in near weekly routine, investigations in the underlying protein-biochemical processes that transiently tailor SOX2 activity to situational demand are underrepresented and have not yet been comprehensively summarized. Largely unrecognizable to modern array or sequencing-based technology, various protein secondary modifications and concomitant function modulations have been reported for SOX2. The chemical modifications imposed onto SOX2 are inherently heterogeneous, comprising singular or clustered events of phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, PARPylation, and O-glycosylation that reciprocally affect each other and critically impact SOX2 functionality, often in a tissue and species-specific manner. One recurring regulatory principle though is the canonical PI3K/AKT signaling axis to which SOX2 relates in various entangled, albeit not exclusive ways. Here we provide a comprehensive review of the current knowledge on SOX2 protein modifications, their proposed relationship to the PI3K/AKT pathway, and regulatory influence on SOX2 with regards to stemness, reprogramming, and cancer.

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“…SOX2 has an important role in regulating early embryonic and normal tissue development, maintaining pluripotency of stem cells and determining cell fate 20,21 . SOX2 is also a potential carcinogenic factor associated with malignancy, lymph node metastasis, and pathological grading and clinical staging, especially in glioma cells, it has a crucial role in maintaining stem cell characteristics 22,23 . Moreover, SOX2 is closely related to tumor chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

LncRNA SOX2OT promotes temozolomide resistance by elevating SOX2 expression via ALKBH5-mediated epigenetic regulation in glioblastoma

Liu¹,

Zhou²,

Wang³

et al. 2020

Cell Death Dis

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Temozolomide (TMZ) resistance is a major cause of recurrence and poor prognosis in glioblastoma (GBM). Recently, increasing evidences suggested that long noncoding RNAs (LncRNAs) modulate GBM biological processes, especially in resistance to chemotherapy, but their role in TMZ chemoresistance has not been fully illuminated. Here, we found that LncRNA SOX2OT was increased in TMZ-resistant cells and recurrent GBM patient samples, and abnormal expression was correlated with high risk of relapse and poor prognosis. Knockdown of SOX2OT suppressed cell proliferation, facilitated cell apoptosis, and enhanced TMZ sensitivity. In addition, we identified that SOX2OT regulated TMZ sensitivity by increasing SOX2 expression and further activating the Wnt5a/β-catenin signaling pathway in vitro and in vivo. Mechanistically, further investigation revealed that SOX2OT recruited ALKBH5, which binds with SOX2, demethylating the SOX2 transcript, leading to enhanced SOX2 expression. Together, these results demonstrated that LncRNA SOX2OT inhibited cell apoptosis, promoted cell proliferation, and TMZ resistance by upregulating SOX2 expression, which activated the Wnt5a/β-catenin signaling pathway. Our findings indicate that LncRNA SOX2OT may serve as a novel biomarker for GBM prognosis and act as a therapeutic target for TMZ treatment.

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Sox2: regulation of expression and contribution to brain tumors

Cited by 32 publications

References 140 publications

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond

LncRNA SOX2OT promotes temozolomide resistance by elevating SOX2 expression via ALKBH5-mediated epigenetic regulation in glioblastoma

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