The DNA-helicase HELLS drives ALK− ALCL proliferation by the transcriptional control of a cytokinesis-related program

Tameni, Annalisa; Sauta, Elisabetta; Mularoni, Valentina; Torricelli, Federica; Manzotti, Gloria; Inghirami, Giorgio; Bellazzi, Riccardo; Fragliasso, Valentina; Ciarrocchi, Alessia

doi:10.1038/s41419-021-03425-0

Cited by 12 publications

(12 citation statements)

References 77 publications

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“…2e ). The gene Hells (also known as Lsh ) encodes a SNF2 family DNA helicase that is required for proliferation of mature T lymphocytes and other cell types 19 , 20 , while Tfdp1 encodes for the transcription factor DP-1 that is involved in G1-S cell cycle progression by forming heterodimers with E2F2 stimulating transcription of numerous E2F-dependent genes 21 . Consistent with upregulation of Hells transcription and activity, several Hells- associated cell cycle genes were upregulated at 16 hr by mIL-2/CD25 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of interleukin-2 receptor signaling

Moro

Wang

et al. 2022

Nat Immunol

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Regulatory T cells (Tregs) require (interleukin-2) IL-2 for their homeostasis by affecting their proliferation, survival, and activation. Here we investigated transcriptional and epigenetic changes after acute, periodic, and persistent IL-2 receptor (IL-2R) signaling in murine peripheral Tregs in vivo using IL-2 or the long-acting IL-2-based biologic mouse IL-2/CD25. We show that initially IL-2R-dependent STAT5 transcription factor-dependent pathways enhanced gene activation, chromatin accessibility, and metabolic reprogramming to support Treg proliferation. Unexpectedly, at peak proliferation, less accessible chromatin prevailed and was associated with Treg contraction. Restimulation of IL-2R signaling after contraction activated signature IL-2-dependent genes and others associated with effector Tregs, whereas genes associated with signal transduction were down-regulated to somewhat temper expansion. Thus, IL-2R-dependent Treg homeostasis depends in part on a shift from more accessible chromatin and expansion to less accessible chromatin and contraction. Mouse IL-2/CD25 supported greater expansion and a more extensive transcriptional state than IL-2 in Tregs, consistent with greater efficacy to control autoimmunity.

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Section: Resultsmentioning

confidence: 99%

Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of interleukin-2 receptor signaling

Moro

Wang

et al. 2022

Nat Immunol

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“…As a member of the GPRIN family, GPRIN1 acts on the classical G protein-coupled receptor pathway [ 46 ]. GPRIN1 is closely related to cancer, and it can promote the proliferation and metastasis of lung cancer by promoting the epithelial-mesenchymal transition of lung cancer cells [ 47 ]. But interestingly, Zhou et al found that GPRIN1 is downregulated in gastric cancer cells and tissues, and it can inhibit the invasion and metastasis of gastric cancer [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Construction and Analysis of Hepatocellular Carcinoma Prognostic Model Based on Random Forest

Wang

Xue

et al. 2023

Canadian Journal of Gastroenterology and Hepatology

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Introduction and Aims. Hepatocellular carcinoma (HCC) is one of the most lethal tumors of the digestive system, but its mechanisms remain unclear. The purpose of this study was to study HCC-related genes, build a survival prognosis prediction model, and provide references for treatment and mechanism research. Methods. Transcriptome data and clinical data of HCC were downloaded from the TCGA database. Screen important genes based on the random forest method, combined with differential expression genes (DEGs) to screen out important DEGs. The Kaplan‒Meier curve was used to evaluate its prognostic significance. Cox regression analysis was used to construct a survival prognosis prediction model, and the ROC curve was used to verify it. Finally, the mechanism of action was explored through GO and KEGG pathway enrichment and GeneMANIA coexpression analyses. Results. Seven important DEGs were identified, three were highly expressed and four were lowly expressed. Among them, GPRIN1, MYBL2, and GSTM5 were closely related to prognosis ( P < 0.05 ). After the survival prognosis prediction model was established, the survival analysis showed that the survival time of the high-risk group was significantly shortened ( P < 0.001 ), but the ROC analysis indicated that the model was not superior to staging. Twenty coexpressed genes were screened, and enrichment analysis indicated that glutathione metabolism was an important mechanism for these genes to regulate HCC progression. Conclusion. This study revealed the important DEGs affecting HCC progression and provided references for clinical assessment of patient prognosis and exploration of HCC progression mechanisms through the construction of predictive models and gene enrichment analysis.

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“…We showed that the loss of BlackMamba or HELLS leads to a significant inhibition of cell proliferation in ALK -ALCL which is associated with slow rate of duplication and by the increase of multinucleated cells (109). Indeed, these cells showed partial defects in central spindle organization and dramatic defects in cleavage furrow formation impacting on cytokinesis completion (110). This phenotype, strictly attributable to HELLS-dependent regulation of Rho-GTPases, underlines the not always recognized fact that cytoskeleton is not only required for cell shape and movement but it is crucial also for cell cycle progression and proliferation.…”

Section: Stat Signaling and Cytoskeleton Regulation In Ptclsmentioning

confidence: 90%

Cytoskeleton Dynamics in Peripheral T Cell Lymphomas: An Intricate Network Sustaining Lymphomagenesis

et al. 2021

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Defects in cytoskeleton functions support tumorigenesis fostering an aberrant proliferation and promoting inappropriate migratory and invasive features. The link between cytoskeleton and tumor features has been extensively investigated in solid tumors. However, the emerging genetic and molecular landscape of peripheral T cell lymphomas (PTCL) has unveiled several alterations targeting structure and function of the cytoskeleton, highlighting its role in cell shape changes and the aberrant cell division of malignant T cells. In this review, we summarize the most recent evidence about the role of cytoskeleton in PTCLs development and progression. We also discuss how aberrant signaling pathways, like JAK/STAT3, NPM-ALK, RhoGTPase, and Aurora Kinase, can contribute to lymphomagenesis by modifying the structure and the signaling properties of cytoskeleton.

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The DNA-helicase HELLS drives ALK− ALCL proliferation by the transcriptional control of a cytokinesis-related program

Cited by 12 publications

References 77 publications

Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of interleukin-2 receptor signaling

Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of interleukin-2 receptor signaling

Construction and Analysis of Hepatocellular Carcinoma Prognostic Model Based on Random Forest

Cytoskeleton Dynamics in Peripheral T Cell Lymphomas: An Intricate Network Sustaining Lymphomagenesis

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