MEF2 plays a significant role in the tumor inhibitory mechanism of encapsulated RENCA cells via EGF receptor signaling in target tumor cells

Martis, Prithy C.; Dudley, Atira; Bemrose, Melissa A.; Gazda, Hunter L.; Smith, Barry H.; Gazda, Lawrence S.

doi:10.1186/s12885-018-5128-5

Cited by 9 publications

(4 citation statements)

References 35 publications

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“…Shengyu Yang, Chenbo Zeng, David Lyden, David Cohen, Larry Gazda and Hans Acha-Orbea, respectively. These cells were cultured as previously described ( Chen et al, 2010 ; Costa-Silva et al, 2015 ; Ersoy et al, 2018 ; Fuertes Marraco et al, 2012 ; Han et al, 2016 ; Huang et al, 2015 ; Martis et al, 2018 ; McDonald et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity

et al. 2021

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SUMMARY Fascin protein is the main actin-bundling protein in filopodia and invadopodia, which are critical for tumor cell migration, invasion, and metastasis. Small-molecule fascin inhibitors block tumor invasion and metastasis and increase the overall survival of tumor-bearing mice. Here, we report a finding that fascin blockade additionally reinvigorates anti-tumor immune response in syngeneic mouse models of various cancers. Fascin protein levels are increased in conventional dendritic cells (cDCs) in the tumor microenvironment. Mechanistically, fascin inhibitor NP-G2–044 increases the number of intratumoral-activated cDCs and enhances the antigen uptake by cDCs. Furthermore, together with PD-1 blocking antibody, NP-G2–044 markedly increases the number of activated CD8 + T cells in the otherwise anti-PD-1 refractory tumors. Reduction of fascin levels in cDCs, but not fascin gene knockout in tumor cells, mimics the anti-tumor immune effect of NP-G2–044. These data demonstrate that fascin inhibitor NP-G2–044 simultaneously limits tumor metastasis and reinvigorates anti-tumor immune responses.

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Section: Methodsmentioning

confidence: 99%

Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity

et al. 2021

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“…MEF2A has been reported to be related to the cell cycle and apoptosis [ 59 ], as also validated by Western blotting in our study. The interaction of the MEF2 family with EGFR inhibits cell proliferation in drug-resistant metastatic colorectal cancer [ 60 ]. In our study, the expression of MEF2A was significantly reduced in the NSCLC tissues and the serum exosomes of patients with gefitinib resistance, which is consistent with the RNA-seq data in TCGA.…”

Section: Discussionmentioning

confidence: 99%

Exosome-derived circKIF20B suppresses gefitinib resistance and cell proliferation in non-small cell lung cancer

Wei

Sun

et al. 2023

Cancer Cell Int

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Background The gefitinib resistance mechanism in non-small cell lung cancer (NSCLC) remains unclear, albeit exosomal circular RNA (circRNA) is known to possibly play a vital role in it. Methods We employed high-throughput sequencing techniques to detect the expressions of exosomal circRNA both in gefitinib-resistant and gefitinib-sensitive cells in this study. The circKIF20B expression was determined in serum exosomes and tissues of patients by qRT-PCR. The structure, stability, and intracellular localization of circKIF20B were verified by Sanger sequencing, Ribonuclease R (RNase R)/actinomycin D (ACTD) treatments, and Fluorescence in situ hybridization (FISH). The functions of circKIF20B were investigated by 5-Ethynyl-20-deoxyuridine (EdU), flow cytometry, Cell Counting Kit-8 (CCK-8), oxygen consumption rate (OCR), and xenograft model. Co-culture experiments were performed to explore the potential ability of exosomal circKIF20B in treating gefitinib resistance. The downstream targets of circKIF20B were determined by luciferase assay, RNA pulldown, and RNA immunoprecipitation (RIP). Results We found that circKIF20B was poorly expressed in the serum exosomes of gefitinib-resistant patients (n = 24) and the tumor tissues of patients with NSCLC (n = 85). CircKIF20B was negatively correlated with tumor size and tumor stage. Decreasing circKIF20B was found to promote gefitinib resistance by accelerating the cell cycle, inhibiting apoptosis, and enhancing mitochondrial oxidative phosphorylation (OXPHOS), whereas increasing circKIF20B was found to restore gefitinib sensitivity. Mechanistically, circKIF20B is bound to miR-615-3p for regulating the MEF2A and then altering the cell cycle, apoptosis, and mitochondrial OXPHOS. Overexpressing circKIF20B parental cells can restore sensitivity to gefitinib in the recipient cells by upregulating the exosomal circKIF20B expression. Conclusions This study revealed a novel mechanism of circKIF20B/miR-615-3p/MEF2A signaling axis involving progression of gefitinib resistance in NSCLC. Exosomal circKIF20B is expected to be an easily accessible and alternative liquid biopsy candidate and potential therapeutic target in gefitinib-resistant NSCLC. Graphical Abstract

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“…The protocol for fixing adherent cells was adapted by Martis et al ( 25 ) with slight modifications. In brief, RAW264.7 cells were grown in 24-well plates treated with LPS, S. anginosus , or S. mitis for 6 h or 24 h with the MOI of 1, 10, or 50.…”

Section: Methodsmentioning

confidence: 99%

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages

Senthil Kumar,

Gunda,

Reinartz

et al. 2024

Infect Immun

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Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis, periodontal disease, and oral cancer. Specifically, Streptococcus anginosus is associated with esophageal, gastric, and pharyngeal cancers, while Streptococcus mitis is linked to oral cancer. However, no study has investigated the mechanistic links between these Streptococcus species and cancer-related inflammatory responses. As an initial step, we probed the innate immune response triggered by S. anginosus and S. mitis in RAW264.7 macrophages. These bacteria exerted time- and dose-dependent effects on macrophage morphology without affecting cell viability. Compared with untreated macrophages, macrophages infected with S. anginosus exhibited a robust proinflammatory response characterized by significantly increased levels of inflammatory cytokines and mediators, including TNF, IL-6, IL-1β, NOS2, and COX2, accompanied by enhanced NF-κB activation. In contrast, S. mitis -infected macrophages failed to elicit a robust inflammatory response. Seahorse Xfe96 analysis revealed an increased extracellular acidification rate in macrophages infected with S. anginosus compared with S. mitis . At the 24-h time point, the presence of S. anginosus led to reduced extracellular itaconate, while S. mitis triggered increased itaconate levels, highlighting distinct metabolic profiles in macrophages during infection in contrast to aconitate decarboxylase expression observed at the 6-h time point. This initial investigation highlights how S. anginosus and S. mitis , two Gram-positive bacteria from the same genus, can prompt distinct immune responses and metabolic shifts in macrophages during infection. IMPORTANCE The surge in head and neck cancer cases among individuals devoid of typical risk factors such as Human Papilloma Virus (HPV) infection and tobacco and alcohol use sparks an argumentative discussion around the emerging role of oral microbiota as a novel risk factor in oral squamous cell carcinoma (OSCC). While substantial research has dissected the gut microbiome’s influence on physiology, the oral microbiome, notably oral streptococci, has been underappreciated during mucosal immunopathogenesis. Streptococcus anginosus , a viridans streptococci group, has been linked to abscess formation and an elevated presence in esophageal cancer and OSCC. The current study aims to probe the innate immune response to S. anginosus compared with the early colonizer Streptococcus mitis as an important first step toward understanding the impact of distinct oral Streptococcus species on the host immune response, which is an understudied determinant of OSCC development and progression.

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MEF2 plays a significant role in the tumor inhibitory mechanism of encapsulated RENCA cells via EGF receptor signaling in target tumor cells

Cited by 9 publications

References 35 publications

Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity

Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity

Exosome-derived circKIF20B suppresses gefitinib resistance and cell proliferation in non-small cell lung cancer

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages

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