A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas

Gehlhausen, Jeffrey R.; Hawley, Eric; Wahle, Benjamin M.; He, Yongzheng; Edwards, Donna; Rhodes, Steven D.; Lajiness, Jacquelyn D.; Staser, Karl; Chen, Shi; Yang, Xianlin; Yuan, Jin; Li, Xiaohong; Jiang, Li; Smith, Abbi E.; Bessler, Waylan; Sandusky, George E.; Stemmer‐Rachamimov, Anat; Stuhlmiller, Timothy J.; Johnson, Gary L.; Nalepa, Grzegorz; Yates, Charles W.; Park, Su-Jung

doi:10.1093/hmg/ddy361

Cited by 7 publications

(6 citation statements)

References 37 publications

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“…Studies have shown that merlin negatively regulates NF-κB signaling, and the elevated NF-κB signal was considered as the hub of the interaction network of aberrant expressed molecules in VS pathobiology ( 29 , 30 , 108 ). In the absence of merlin, overexpressed NIK and IKKα induced high NF-κB dependent transcription ( 29 ), while merlin expression blocks NF-κB activation by the inhibition of p65, NIK, IKKα, tumor necrosis factor-α (TNF-α)-induced IκB degradation, NF-κB–DNA binding and endogenous NF-κB signaling ( 30 ).…”

Section: Resultsmentioning

confidence: 99%

“…Besides, activated NF-κB is thought to be the mechanism by which elevated p75 NTR expression promotes cell survival in VS ( 109 ). Hyper NF-κB activity in VS potentiated hepatocyte growth factor (HGF) to c-Met autocrine feed-forward loop to promote tumor cell proliferation ( 108 ), and increased the expression of factors that reported to be increased in VS or correlated with the prognosis or absolute tumor growth rate of VS, such as matrix metalloproteinase 2 (MMP-2), MMP-9 ( 40 ), MMP-14 ( 41 ), COX-2 ( 110 ), interleukin-1 (IL-1), IL-6, TNF-α ( 64 ) and signal transducers and activators of transcription 1 (STAT1) ( 111 ).…”

Section: Resultsmentioning

confidence: 99%

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Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects

et al. 2021

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Vestibular schwannomas (VSs, also known as acoustic neuromas) are relatively rare benign brain tumors stem from the Schwann cells of the eighth cranial nerve. Tumor growth is the paramount factor for neurosurgeons to decide whether to choose aggressive treatment approach or careful follow-up with regular magnetic resonance imaging (MRI), as surgery and radiation can introduce significant trauma and affect neurological function, while tumor enlargement during long-term follow-up will compress the adjacent nerves and tissues, causing progressive hearing loss, tinnitus and vertigo. Recently, with the deepening research of VS biology, some proteins that regulate merlin conformation changes, inflammatory cytokines, miRNAs, tissue proteins and cerebrospinal fluid (CSF) components have been proposed to be closely related to tumor volume increase. In this review, we discuss advances in the study of biomarkers that associated with VS growth, providing a reference for exploring the growth course of VS and determining the optimal treatment strategy for each patient.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects

et al. 2021

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“…Several studies demonstrated that NSAIDs were not associated with the growth of vestibular schwannoma [ 65 , 66 , 67 ]. Aspirin can also suppress the NF-κB pathway in vestibular schwannoma, leading to another mechanism of treatment [ 68 , 69 ]. Although there is still debate on the matter, aspirin may be used for a “wait and scan” approach for patients with vestibular schwannoma [ 70 ].…”

Section: Schwannomamentioning

confidence: 99%

Drug Repositioning for Refractory Benign Tumors of the Central Nervous System

Tamura

2023

IJMS

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Drug repositioning (DR) is the process of identifying novel therapeutic potentials for already-approved drugs and discovering new therapies for untreated diseases. DR can play an important role in optimizing the pre-clinical process of developing novel drugs by saving time and cost compared with the process of de novo drug discovery. Although the number of publications related to DR has rapidly increased, most therapeutic approaches were reported for malignant tumors. Surgical resection represents the definitive treatment for benign tumors of the central nervous system (BTCNS). However, treatment options remain limited for surgery-, chemotherapy- and radiation-refractory BTCNS, as well as malignant tumors. Meningioma, pituitary neuroendocrine tumor (PitNET), and schwannoma are the most common BTCNS. The treatment strategy using DR may be applied for refractory BTCNS, such as Grade 2 meningiomas, neurofibromatosis type 2-related schwannomatosis, and PitNETs with cavernous sinus invasion. In the setting of BTCNS, stable disease can provide significant benefit to the patient. DR may provide a longer duration of survival without disease progression for patients with refractory BTCNS. This article reviews the utility of DR for refractory BTCNS.

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“…NF-κB is a ubiquitous transcription factor central to cell growth, apoptosis, inflammation, and various malignant diseases (25). Researchers have found that the Merlin protein negatively regulates NF-κB signaling, and an elevated NF-κB signal is considered as the hub of the interaction network of aberrantly expressed molecules in VS pathobiology (14,26,27). Therefore, we examined the NF-κB expression, and as shown in Fig.…”

Section: Protein and Rna Expression Of β 2 -M In Tumor Tissuesmentioning

confidence: 99%

β2-Microglobulin Participates in the Development of Vestibular Schwannoma by Regulating Nuclear Factor-κB

et al. 2022

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Background and Objectives: Vestibular schwannoma (VS), the most common intercranial schwannoma, originates from the sheath of the vestibular nerve. The growth rate of VS varies greatly, with the tumor enlarging gradually, which can compress the peripheral nerve tissue and reveal corresponding symptoms. This study was aimed to elucidate the growth mechanism of VS by analyzing cellular changes at protein, messenger ribonucleic acid (mRNA), and other molecular levels. Methods: We determined mRNA and protein levels of β 2 -microglobulin (β 2 -M) and nuclear factor κB (NF-κB) in tumors of different sizes using the real-time polymerase chain reaction and Western blotting, respectively. The relationship between these factors was verified in VS primary cells cultured in vitro, and the potential role of β 2 -M and NF-κB in VS growth was elucidated.Results: In the secretions of freshly isolated tumor tissue cultured for 72 h, the concentration of β 2 -M was positively correlated with the tumor diameter. Furthermore, tumors with larger diameter showed higher expressions of β 2 -M and NF-κB at protein and mRNA level. β 2 -M treatment resulted in elevated protein expression of NF-κB and also its phosphorylated form in vitro. Conclusion: β 2 -M may participate in VS growth by regulating NF-κB and act as a key regulatory molecule in VS tumor growth.

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A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas

Cited by 7 publications

References 37 publications

Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects

Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects

Drug Repositioning for Refractory Benign Tumors of the Central Nervous System

β2-Microglobulin Participates in the Development of Vestibular Schwannoma by Regulating Nuclear Factor-κB

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