N-cadherin upregulation mediates adaptive radioresistance in glioblastoma

Osuka, Satoru; Zhu, Dan; Zhang, Zhaobin; Li, Chaoxi; Stackhouse, Christian T.; Sampetrean, Oltea; Olson, Jeffrey J.; Gillespie, G. Yancey; Saya, Hideyuki; Willey, Christopher D.; Meir, Erwin G. Van

doi:10.1172/jci136098

Cited by 45 publications

(21 citation statements)

References 72 publications

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“…Gliomas account for more than 60% of primary intracranial tumors [ 35 ]. Due to its aggressive nature and unclear boundaries, it is difficult to remove completely these tumors with surgery alone [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

et al. 2022

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Glioma is one of the leading causes of tumor-related deaths worldwide, but its potential mechanism remains unclear. This study aimed to explore the biological role and potential mechanism of argininosuccinate synthase 1 (ASS1) in glioma. The relative expression levels of ASS1 in glioma specimens and cell lines were calculated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The biological functions of ASS1 were demonstrated using the 5-ethynyl-2ʹ-deoxyuridine (EdU) assay, transwell assay, and in vivo experiments. In addition, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanism of ASS1 in glioma. ASS1 expression levels were found to be downregulated in glioma specimens and cell lines. Functionally, we confirmed that ASS1 inhibited glioma cell proliferation, migration, invasion, and growth both. Furthermore, we found that ASS1 was a target of N(6)-adenosine-methyltransferase-14 (METTL14)-mediated N 6 -methyladenosine (m 6 A) modification. Overexpression of METTL14 markedly elevated ASS1 mRNA m 6 A modification and suppressed ASS1 mRNA expression. We also revealed that METTL14-mediated ASS1 mRNA degradation relied on the YTH m6A RNA-binding protein 2 (YTHDF2)-dependent pathway. We confirmed that decreased ASS1 expression promoted the cell proliferation, migration, and invasion in glioma, and that the METTL14/ASS1/YTHDF2 regulatory axis may be an effective therapeutic target for glioma.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

et al. 2022

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“…We showed that the proneural-to-mesenchymal transition is independent of histological feature composition and reflects transcriptional changes in the cellular tumor. Mesenchymal transitions have been shown to associate with several factors, including increased myeloid cell infiltration, radiation-induced NF-κB activation, altered tumor metabolism, and hypoxia (Bhat et al, 2013;Garofano et al, 2021;Kim et al, 2021;Mao et al, 2013;Osuka et al, 2021;Schmitt et al, 2021;Wang et al, 2017). Our results indicate that the proneural-tomesenchymal transition is likely influenced by tumor-wide changes, supporting the hypothesis that this transition is involved in therapy resistance.…”

Section: Discussionsupporting

confidence: 77%

Longitudinal analysis of diffuse glioma reveals cell state dynamics at recurrence associated with changes in genetics and the microenvironment

Varn

Johnson

Wade

et al. 2021

Preprint

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To interrogate the factors driving therapy resistance in diffuse glioma, we collected and analyzed RNA and/or DNA sequencing data from temporally separated tumor pairs of 292 adult patients with IDH-wild-type or IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions associated with an increase in proliferating stem-like malignant cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their malignant cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a specific myeloid cell state defined by unique ligand-receptor interactions with malignant cells. Collectively, our results uncover recurrence-associated changes that could be targetable to shape disease progression following initial diagnosis.

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“…To identify the factors that determine the radioresistance of HGGs, human and murine radioresistant GICs were generated by exposing them to repeated irradiation cycles [30]. The acquired radio resistance was accompanied by a reduction in proliferative capacity as well as an increase in intercellular adhesion and N-cadherin expression.…”

Section: Advances In Rtmentioning

confidence: 99%

“…Conversely, radioresistant GICs lost their acquired phenotype, following CRISPR/Cas9 knockout of N-cadherin. In turn, N-cadherin overexpression was stimulated by the radiation-induced secretion of insulin-like growth factor 1 [30].…”

Section: Advances In Rtmentioning

confidence: 99%

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

Fròsina

2021

IJMS

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Albeit the effort to develop targeted therapies for patients with high-grade gliomas (WHO grades III and IV) is evidenced by hundreds of current clinical trials, radiation remains one of the few effective therapeutic options for them. This review article analyzes the updates on the topic “radiotherapy of high-grade gliomas” during the period 1 January 2021–30 June 2021. The high number of articles retrieved in PubMed using the search terms (“gliom* and radio*”) and manually selected for relevance indicates the feverish research currently ongoing on the subject. During the last semester, significant advances were provided in both the preclinical and clinical settings concerning the diagnosis and prognosis of high-grade gliomas, their radioresistance, and the inevitable side effects of their treatment with radiation. The novel information concerning tumor radiosensitization was of special interest in terms of therapeutic perspective and was discussed in detail.

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N-cadherin upregulation mediates adaptive radioresistance in glioblastoma

Cited by 45 publications

References 72 publications

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

Longitudinal analysis of diffuse glioma reveals cell state dynamics at recurrence associated with changes in genetics and the microenvironment

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

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