NAB2-STAT6 fusion protein mediates cell proliferation and oncogenic progression via EGR-1 regulation

Park, Ye-Seul; Kim, Hyeng-Soo; Kim, Ju-Heon; Choi, Sang-Bang; Kim, Dasom; Ryoo, Zae Young; Lee, Sanggyu

doi:10.1016/j.bbrc.2020.03.090

Cited by 23 publications

(17 citation statements)

References 19 publications

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“…They also determined that pan-TRK protein overexpression in SFT was mainly attributable to the upregulation of NTRK1 mRNA. Since NTRK1 is a target of EGR1, the central hub involved in NAB2-STAT6-dependent deregulation of gene expression [10,38], our results may suggest that an increased EGR1 transcriptional program could lead to a more aggressive tumor phenotype. This correlation has been not reported before and deserves further confirmation.…”

Section: Analysis Of Additional Molecular Markersmentioning

confidence: 88%

Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

Salguero-Aranda

Martínez-Reguera

Marcilla

et al. 2021

Cancers

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Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this entity has increased in recent years, new molecular alterations have emerged that could be helpful to refine current risk models. Here, we evaluated NAB2-STAT6 fusion variants and other molecular alterations in a series of 83 SFTs that are enriched in progressing cases. Gene fusion variants were identified by targeted RNA-seq in the whole series, whereas TERT promoter (pTERT) mutations were inspected by Sanger sequencing in a subset of 18 cases. Immunohistochemical assays were performed to assess BCOR and NTRK expression as well as P53 mutation status in 45, 44, and 44 cases, respectively. While confirming the associations of gene fusion variants with clinicopathological parameters, our results do not prove their prognostic value. Pan-TRK immunoexpresion correlated with recurrence/progression, P53 staining associated with higher mitotic counts, and pTERT mutations were enriched in cases with fatal outcome. An intriguing correlation was found for BCOR protein expression with gene fusion variants, size, and tumor location.

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Section: Analysis Of Additional Molecular Markersmentioning

confidence: 88%

Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

Salguero-Aranda

Martínez-Reguera

Marcilla

et al. 2021

Cancers

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“…The Egr-1 gene, as a member of the zinc finger structure transcription factor family, is located on human chromosome 5q31 and encodes a DNA-binding transcription factor of ~80 kDa (39). It has been demonstrated that Egr-1 serves an important role in cell growth, differentiation and apoptosis (16,(40)(41)(42)(43)(44). At the same time, Egr-1 is closely associated with the occurrence and development of certain diseases, for example tutor and leukemia, however the specific signaling pathway of each of them remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

Wang

Zhao

et al. 2022

Oncol Lett

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“…Surprisingly, EGR1 was found to be overexpressed under combinatorial treatment though its overexpression is recognised to be driven by the pathognomonic NAB2-STAT6 gene fusion. The gene fusion hijacks NAB2 interaction with EGR1 by cleaving off its inhibitory domain and fusing on a transactivating domain from STAT6, altering its function from inhibitory to constitutively active (69). We postulate that overexpression of EGR1 as a result of combinatorial treatment contributes to increased apoptosis, as shown in other publications which demonstrated the role of EGR1 overexpression in mediating apoptotic cell fates in both neurons and cancers (45,70).…”

Section: Discussionmentioning

confidence: 99%

Ex vivo drug testing in an ultra-rare sarcoma reveals therapeutic vulnerability and resistance

Chan

Luo

Chen

et al. 2022

Preprint

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Solitary fibrous tumors (SFTs) are rare soft tissue sarcomas for which therapeutic options are limited and ineffective. We successfully demonstrated how functional personalized treatment was implemented in the clinic for an ultra-rare sarcoma with otherwise limited options, through a combined strategy of patient-derived model development and computational drug analytics. Molecular profiling of tumours and patient-derived models uncovered potential biomarkers to predict responses to specific drugs. We generated patient-derived SFT cells (PDSC) and used a computational combinatorial drug screening analytics platform, Quadratic Phenotypic Optimization Platform (QPOP), to determine therapeutic vulnerability and resistance in an ultra-rare locally recurrent brain SFT and its distant liver metastasis. QPOP derived and ranked the efficacy of 531,441 drug combinations, revealing BETi-pazopanib synergy in the liver lesion that outperforms standard-of-care combination doxorubicin-ifosfamide, which was antagonistic. In tumour and PDSC from the pazopanib-resistant brain lesion, transcriptomic analyses identified the UGT1A family as potential biomarkers of pazopanib resistance. Eribulin sensitivity was predicted to be shared across both lesions. Our patient was therefore treated with eribulin and successfully gained clinically meaningful disease control.

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NAB2-STAT6 fusion protein mediates cell proliferation and oncogenic progression via EGR-1 regulation

Cited by 23 publications

References 19 publications

Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

Ex vivo drug testing in an ultra-rare sarcoma reveals therapeutic vulnerability and resistance

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