Identification of new ETV6 modulators through a high-throughput functional screening

Neveu, Benjamin; Richer, Chantal; Cassart, Pauline; Caron, Maxime; Jimenez-Cortes, Camille; St-Onge, Pascal; Fuchs, Claire; Garnier, Nicolas; Gobeil, Stéphane; Sinnett, Daniel

doi:10.1016/j.isci.2022.103858

Cited by 4 publications

(3 citation statements)

References 67 publications

(106 reference statements)

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“…Loss of ETV6 function is associated with the development of hematological cancers. Using a functional genome-wide shRNA screen, researchers discovered that COMMD9 -knockdown in leukemic cells might inhibit ETV6 transcriptional activity ( 89 ). However, the underlying mechanism by which COMMD9 regulates ETV6 remains unknown.…”

Section: The Commd Protein Family and Tumorsmentioning

confidence: 99%

COMMD proteins function and their regulating roles in tumors

et al. 2023

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The COMMD proteins are a highly conserved protein family with ten members that play a crucial role in a variety of biological activities, including copper metabolism, endosomal sorting, ion transport, and other processes. Recent research have demonstrated that the COMMD proteins are closely associated with a wide range of disorders, such as hepatitis, myocardial ischemia, cerebral ischemia, HIV infection, and cancer. Among these, the role of COMMD proteins in tumors has been thoroughly explored; they promote or inhibit cancers such as lung cancer, liver cancer, gastric cancer, and prostate cancer. COMMD proteins can influence tumor proliferation, invasion, metastasis, and tumor angiogenesis, which are strongly related to the prognosis of tumors and are possible therapeutic targets for treating tumors. In terms of molecular mechanism, COMMD proteins in tumor cells regulate the oncogenes of NF-κB, HIF, c-MYC, and others, and are related to signaling pathways including apoptosis, autophagy, and ferroptosis. For the clinical diagnosis and therapy of malignancies, additional research into the involvement of COMMD proteins in cancer is beneficial.

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Section: The Commd Protein Family and Tumorsmentioning

confidence: 99%

COMMD proteins function and their regulating roles in tumors

et al. 2023

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“…While DYRK3 reprogramed hepatocellular carcinoma metabolism by negatively regulating nuclear receptor coactivator 3/activating transcription factor 4 transcription factor complex 28 . Neveu et al found that DYRK4 knockdown led to abrogation of ETV6 repressive activity, through which it could participate in cellular transformation in hematological malignancies 29 . We further checked the literatures about the DYRK family members.…”

Section: Introductionmentioning

confidence: 99%

“…28 Neveu et al found that DYRK4 knockdown led to abrogation of ETV6 repressive activity, through which it could participate in cellular transformation in hematological malignancies. 29 We further checked the literatures about the DYRK family members.…”

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confidence: 99%

Hypomethylation of DYRK4 in peripheral blood is associated with increased lung cancer risk

Qiao,

Zhu,

et al. 2023

Molecular Carcinogenesis

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Lung cancer (LC) is the leading cause of cancer‐related deaths worldwide. It is urgent to identify new biomarkers for the early detection of LC. DNA methylation in peripheral blood has been reported to be associated with cancers. We conducted two independent case–control studies and a nested case–control study (168 LC cases and 167 controls in study Ⅰ, 677 LC cases and 833 controls in study Ⅱ, 147 precancers and 21 controls in the nested case–control study). The methylation levels of DYRK4 CpG sites were measured using mass spectrometry and their correlations with LC were analyzed by logistic regression and nonparametric tests. Bonferroni correction was used for the multiple comparisons. LC‐related decreased DYRK4 methylation was discovered in Study I and validated in Study II (the odds ratios [ORs] for the lowest vs. highest quartile of all three DYRK4 CpG sites ranged from 1.64 to 2.09, all p < 0.001). Combining the two studies, hypomethylation of DYRK4 was observed in stage I cases (ORs per −10% methylation ranged from 1.16 to 1.38, all p < 5.9E−04), and could be enhanced by male gender (ORs ranged from 1.77 to 4.17 via interquartile analyses, all p < 0.017). Hypomethylation of DYRK4_A_CpG_2 was significantly correlated with tumor size, length, and stage (p = 0.034, 0.002, and 0.002, respectively) in LC cases. Our study disclosed the association between DYRK4 hypomethylation in peripheral blood and LC, suggesting the feasibility of blood‐based DNA methylation as new biomarker for LC detection.

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The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21)

Kaczmarska

Derebas

Pinkosz

et al. 2023

Cells

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The most frequent chromosomal rearrangement in childhood B-cell acute lymphoblastic leukemia (B-ALL) is translocation t(12;21)(p13;q22). It results in the fusion of the ETV6::RUNX1 gene, which is active in the regulation of multiple crucial cellular pathways. Recent studies hypothesize that many translocations are influenced by RAG-initiated deletions, as well as defects in the RAS and NRAS pathways. According to a “two-hit” model for the molecular pathogenesis of pediatric ETV6::RUNX1-positive B-ALL, the t(12;21) translocation requires leukemia-causing secondary mutations. Patients with ETV6::RUNX1 express up to 60 different aberrations, which highlights the heterogeneity of this B-ALL subtype and is reflected in differences in patient response to treatment and chances of relapse. Most studies of secondary genetic changes have concentrated on deletions of the normal, non-rearranged ETV6 allele. Other predominant structural changes included deletions of chromosomes 6q and 9p, loss of entire chromosomes X, 8, and 13, duplications of chromosome 4q, or trisomy of chromosomes 21 and 16, but the impact of these changes on overall survival remains unclarified. An equally genetically diverse group is the recently identified new B-ALL subtype ETV6::RUNX1-like ALL. In our review, we provide a comprehensive description of recurrent secondary mutations in pediatric B-ALL with t(12;21) to emphasize the value of investigating detailed molecular mechanisms in ETV6::RUNX1-positive B-ALL, both for our understanding of the etiology of the disease and for future clinical advances in patient treatment and management.

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Identification of new ETV6 modulators through a high-throughput functional screening

Cited by 4 publications

References 67 publications

COMMD proteins function and their regulating roles in tumors

COMMD proteins function and their regulating roles in tumors

Hypomethylation of DYRK4 in peripheral blood is associated with increased lung cancer risk

The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21)

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