ArticleCell biology and toxicology2023
MMP-9 reinforces radiation-induced delayed invasion and metastasis of neuroblastoma cells through second-signaling positive feedback with NFκB via both ERK and IKK activation.
Article in Cell biology and toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Review
- Engineered N-TIMP2 Variant Specifically Targeting MMP-9 Exhibits Potent Anti-Glioblastoma Activity.Biomolecules · 2025Article
- Nanopuerarin Improves Doxorubicin Therapeutic Efficacy by Inhibiting Angiogenesis via Regulating NSUN2 in Hepatocellular Carcinoma.ACS omega · 2025Article
- Novel endoplasmic reticulum stress-related gene signature unveils CDKN3 as a prognosticator in neuroblastoma.Translational pediatrics · 2025Article
- Review
- FAM201A encodes small protein NBASP to inhibit neuroblastoma progression via inactivating MAPK pathway mediated by FABP5.Communications biology · 2023Article
- Review
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Neuroblastoma (NB) progression is branded with hematogenous metastasis and frequent relapses. Despite intensive multimodal clinical therapy, outcomes for patients with progressive disease remain poor, with negligible long-term survival. Therefore, understanding the acquired molecular rearrangements in NB cells with therapy pressure and developing improved therapeutic strategies is a critical need to improve the outcomes for high-risk NB patients. We investigated the rearrangement of MMP9 in NB with therapy pressure, and unveiled the signaling that facilitates NB evolution. Radiation-treatment (RT) significantly increased MMP9 expression/activity, and the induced enzyme activity was persistently maintained across NB cell lines. Furthermore, RT-triggered NFκB transcriptional activity and this RT-induced NFκB were required/adequate for MMP9 maintenance. RT-triggered NFκB-dependent MMP9 actuated a second-signaling feedback to NFκB, facilitating a NFκB-MMP9-NFκB positive feedback cycle (PFC). Critically, MMP9-NFκB feedback is mediated by MMP9-dependent activation of IKKβ and ERK phosphotransferase activity. Beyond its tumor invasion/metastasis function, PFC-dependent MMP9 lessens RT-induced apoptosis and favors survival pathway through the activation of NFκB signaling. In addition, PFC-dependent MMP9 regulates 19 critical molecular determinants that play a pivotal role in tumor evolution. Interestingly, seven of 19 genes possess NFκB-binding sites, demonstrating that MMP9 regulates these molecules by activating NFκB. Collectively, these data suggest that RT-triggered NFκB-dependent MMP9 actuates feedback to NFκB though IKKβ- and ERK1/2-dependent IκBα phosphorylation. This RT-triggered PFC prompts MMP9-dependent survival advantage, tumor growth, and dissemination. Targeting therapy-pressure-driven PFC and/or selective inhibition of MMP9 maintenance could serve as promising therapeutic strategies for treatment of progressive NB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.