SOX9 expression increases with malignant potential in tumors from patients with neurofibromatosis 1 and is not correlated to desert hedgehog

Carbonnelle-Puscian, Amélie; Vidal, Valérie; Laurendeau, Ingrid; Valeyrie‐Allanore, Laurence; Vidaud, Dominique; Bièche, Ivan; Leroy, Karen; Lantieri, Laurent; Wolkenstein, Pierre; Schedl, Andreas; Ortonne, Nicolas

doi:10.1016/j.humpath.2010.02.020

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…As part of a developmental pathway, elevation of SOX9 in prostate neoplasia promotes tumor cell proliferation [17]. Moreover, as a transcription factor, SOX9 is linked to the hedgehog pathways and may play a role in the development of malignant peripheral nerve sheath tumor in patients [18]. Ling et al reported that despite SOX9 levels being high during periods of prenatal urothelial development in mouse bladders, SOX9 was diminished and quiescent with maturation after birth, but was rapidly induced by a variety of injuries and urothelial cancer [19].…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of SOX9 in human non-small cell lung cancer progression and overall patient survival

Zhou

et al. 2012

J Exp Clin Cancer Res

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BackgroundSex determining region Y (SRY)-related high mobility groupbox 9 (SOX9) is an important transcription factor required for development, which regulates the expression of target genes in the associated pathway. The aim of this study was to describe the expression of SOX9 in human non-small cell lung cancer (NSCLC) and to investigate the association between SOX9 expression and progression of NSCLC.MethodsSOX9 protein and mRNA expression in normal human pneumonocytes, lung cancer cell lines, and eight pairs of matched lung cancer tissues and their adjacent normal lung tissues were detected by Western blotting and real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was used to determine SOX9 protein expression in 142 cases of histologically characterized NSCLC. Statistical analyses were applied to test for prognostic and diagnostic associations.ResultsSOX9 in lung cancer cell lines was upregulated at both mRNA and protein levels, and SOX9 mRNA and protein were also elevated in NSCLC tissues compared with levels in corresponding adjacent non-cancerous lung tissues. Immunohistochemical analysis demonstrated a high expression of SOX9 in 74/142 (52.1%) paraffin-embedded archival lung cancer biopsies. Statistical analysis indicated that upregulation of SOX9 was significantly correlated with the histological stage of NSCLC (P = 0.017) and that patients with a high SOX9 level exhibited a shorter survival time (P < 0.001). Multivariate analysis illustrated that SOX9 upregulation might be an independent prognostic indicator for the survival of patients with NSCLC.ConclusionsThis work shows that SOX9 may serve as a novel and prognostic marker for NSCLC, and play a role during the development and progression of the disease.

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Section: Discussionmentioning

confidence: 99%

Clinical significance of SOX9 in human non-small cell lung cancer progression and overall patient survival

Zhou

et al. 2012

J Exp Clin Cancer Res

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“…SOX9 is expressed in SCs obtained from NF1 tumors and is signi cantly upregulated in MPNST as compared to neuro bromas (22,23). It was once considered a potential target marker for neuro bromas (23).…”

Section: Discussionmentioning

confidence: 99%

“…The expression levels and localization of SOX9 and PCOLCE in neuro broma pathological tissues and cell lines were validated using co-immunoprecipitation (co-IP), immuno uorescent staining, and Western blot analyses. Although the expression level of SOX9 in the neuro broma is well-documented (22,23), the function of SOX9 in regulating cancer cell-derived collagens has not been explored previously in the context of neuro broma development.…”

Section: Introductionmentioning

confidence: 99%

SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma

Yao,

Wang,

et al. 2024

Mol Neurobiol

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Neuro bromatosis type 1 (NF1) is caused by NF1 gene mutations. Patients with NF1 often have complications with tumors, such as neuro broma. In order to investigate the pathogenesis of human neuro broma, a systematic comparison of protein expression levels between Schwann cell-like sNF96.2 cells, originating from malignant peripheral nerve sheath tumors (MPNST), and normal Schwann cells was performed using 4-D label-free proteomic analysis. In addition, the expression levels and localization of dysregulated proteins were con rmed using a Gene Expression Omnibus (GEO) transcriptomic dataset, Western blot analysis, and immuno uorescence labeling. The effects of SRY-box transcription factor 9 (SOX9) in the neuro broma and surrounding microenvironment were evaluated in vivo using a tumor transplantation model. The present study observed that SOX9 and procollagen Cendopeptidase enhancer (PCOLCE) were signi cantly altered. NF1 mutation promoted the nuclear translocation and transcriptional activity of SOX9 in neuro bromas. SOX9 increased collagen VI secretions by enhancing the activation of PCOLCE in neuro broma cells. These ndings might provide new perspectives on the pathophysiological signi cance of SOX9 in neuro bromas and elucidate a novel molecular mechanism underlying neuro bromas.

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“…DLX5 has been shown to promote lung cancers by transcriptionally activating MYC [73]. SOX9 has been identified as a survival gene and marker in neurofibromatosis tumors, with increased expressions in malignant tumors [7,51].…”

Section: Discussionmentioning

confidence: 99%

Enhancer reprogramming in PRC2-deficient malignant peripheral nerve sheath tumors induces a targetable de-differentiated state

et al. 2021

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Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that frequently harbor genetic alterations in polycomb repressor complex 2 (PRC2) components-SUZ12 and EED. Here, we show that PRC2 loss confers a dedifferentiated early neural-crest phenotype which is exclusive to PRC2-mutant MPNSTs and not a feature of neurofibromas. Neural crest phenotype in PRC2 mutant MPNSTs was validated via cross-species comparative analysis using spontaneous and transgenic MPNST models. Systematic chromatin state profiling of the MPNST cells showed extensive epigenomic reprogramming or chromatin states associated with PRC2 loss and identified gains of active enhancer states/super-enhancers on early neural crest regulators in PRC2-mutant conditions around genomic loci that harbored repressed/poised states in PRC2-WT MPNST cells. Consistently, inverse correlation between H3K27me3 loss and H3K27Ac gain was noted in MPNSTs. Epigenetic editing experiments established functional roles for enhancer gains on DLX5-a key regulator of neural crest phenotype. Consistently, blockade of enhancer activity by bromodomain inhibitors specifically suppressed this neural crest phenotype and tumor burden in PRC2-mutant PDXs. Together, these findings reveal accumulation of dedifferentiated neural crest like state in PRC2-mutant MPNSTs that can be targeted by enhancer blockade.

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SOX9 expression increases with malignant potential in tumors from patients with neurofibromatosis 1 and is not correlated to desert hedgehog

Cited by 8 publications

References 34 publications

Clinical significance of SOX9 in human non-small cell lung cancer progression and overall patient survival

Clinical significance of SOX9 in human non-small cell lung cancer progression and overall patient survival

SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma

Enhancer reprogramming in PRC2-deficient malignant peripheral nerve sheath tumors induces a targetable de-differentiated state

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