Linking human sympathoadrenal development and neuroblastoma

Rohrer, Hermann

doi:10.1038/s41588-021-00845-8

Cited by 21 publications

(16 citation statements)

References 15 publications

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“…The comparison of adrenal NBs classified by risk subgroups with normal sympatho-adrenal cells has further highlighted that tumor severity correlates with neuroblast differentiation grade. Specifically, data indicate that high risk tumors derive from early stages of adrenal neuroblast differentiation trajectory, while low-risk tumors arise later during development [ 45 , 46 , 47 , 48 , 54 ], reflecting the differentiation status of the AM development at the time of the onset of genetic or epigenetic hits.…”

Section: Neuroblastoma: Genetic Determinants and Developmental Originmentioning

confidence: 99%

A Focus on Regulatory Networks Linking MicroRNAs, Transcription Factors and Target Genes in Neuroblastoma

Perri

Ponzoni

Corrias

et al. 2021

Cancers

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Neuroblastoma (NB) is a tumor of the peripheral sympathetic nervous system that substantially contributes to childhood cancer mortality. NB originates from neural crest cells (NCCs) undergoing a defective sympathetic neuronal differentiation and although the starting events leading to the development of NB remain to be fully elucidated, the master role of genetic alterations in key oncogenes has been ascertained: (1) amplification and/or over-expression of MYCN, which is strongly associated with tumor progression and invasion; (2) activating mutations, amplification and/or over-expression of ALK, which is involved in tumor initiation, angiogenesis and invasion; (3) amplification and/or over-expression of LIN28B, promoting proliferation and suppression of neuroblast differentiation; (4) mutations and/or over-expression of PHOX2B, which is involved in the regulation of NB differentiation, stemness maintenance, migration and metastasis. Moreover, altered microRNA (miRNA) expression takes part in generating pathogenetic networks, in which the regulatory loops among transcription factors, miRNAs and target genes lead to complex and aberrant oncogene expression that underlies the development of a tumor. In this review, we have focused on the circuitry linking the oncogenic transcription factors MYCN and PHOX2B with their transcriptional targets ALK and LIN28B and the tumor suppressor microRNAs let-7, miR-34 and miR-204, which should act as down-regulators of their expression. We have also looked at the physiologic role of these genetic and epigenetic determinants in NC development, as well as in terminal differentiation, with their pathogenic dysregulation leading to NB oncogenesis.

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Section: Neuroblastoma: Genetic Determinants and Developmental Originmentioning

confidence: 99%

A Focus on Regulatory Networks Linking MicroRNAs, Transcription Factors and Target Genes in Neuroblastoma

Perri

Ponzoni

Corrias

et al. 2021

Cancers

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“…These studies suggest that the plasticity of Schwann cell precursors is more extensively involved in tissue establishment and regeneration than previously assumed [ 25 ]. Although these findings have increased our understanding of human sympathoadrenal development and given further insight into the heterogeneity of neuroblastoma, the trajectory from developing normal neural crest cells to malignant neuroblastoma is still incomplete [ 36 ].…”

Section: The Neural Crest and Neuroblastoma Cell Of Originmentioning

confidence: 99%

Neuroblastoma Heterogeneity, Plasticity, and Emerging Therapies

2022

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Purpose of Review The evolving information of the initiation, tumor cell heterogeneity, and plasticity of childhood neuroblastoma has opened up new perspectives for developing therapies based on detailed knowledge of the disease. Recent Findings The cellular origin of neuroblastoma has begun to unravel and there have been several reports on tumor cell heterogeneity based on transcriptional core regulatory circuitries that have given us important information on the biology of neuroblastoma as a developmental disease. This together with new insight of the tumor microenvironment which acts as a support for neuroblastoma growth has given us the prospect for designing better treatment approaches for patients with high-risk neuroblastoma. Here, we discuss these new discoveries and highlight some emerging therapeutic options. Summary Neuroblastoma is a disease with multiple facets. Detailed biological and molecular knowledge on neuroblastoma initiation, heterogeneity, and the communications between cells in the tumor microenvironment holds promise for better therapies.

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“…However, the proposed projections from normal developing cells to malignant cells rely on the fundamental premise that the original signature of the founder cell is maintained during tumor initiation and progression [ 15 ]. In view of the developmental plasticity of the chromaffin cells and neuroblasts observed both in vivo and in vitro [ 7 , 16 , 17 , 18 ], adrenal tumor development may involve chromaffin cells that shift towards a neuroblast identity during tumor initiation and progression.…”

Section: Introductionmentioning

confidence: 99%

BET and CDK Inhibition Reveal Differences in the Proliferation Control of Sympathetic Ganglion Neuroblasts and Adrenal Chromaffin Cells

Sriha

Louis‐Brennetot

Pierre-Eugène

et al. 2022

Cancers

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Neuroblastoma arising from the adrenal differ from ganglionic neuroblastoma both genetically and clinically, with adrenal tumors being associated with a more severe prognosis. The different tumor properties may be linked to specific tumor founder cells in adrenal and sympathetic ganglia. To address this question, we first set up cultures of mouse sympathetic neuroblasts and adrenal chromaffin cells. These cultures were then treated with various proliferation inhibitors to identify lineage-specific responses. We show that neuroblast and chromaffin cell proliferation was affected by WNT, ALK, IGF1, and PRC2/EZH2 signaling inhibitors to a similar extent. However, differential effects were observed in response to bromodomain and extraterminal (BET) protein inhibitors (JQ1, GSK1324726A) and to the CDK-7 inhibitor THZ1, with BET inhibitors preferentially affecting chromaffin cells, and THZ1 preferentially affecting neuroblasts. The differential dependence of chromaffin cells and neuroblasts on BET and CDK signaling may indicate different mechanisms during tumor initiation in sympathetic ganglia and adrenal.

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Linking human sympathoadrenal development and neuroblastoma

Cited by 21 publications

References 15 publications

A Focus on Regulatory Networks Linking MicroRNAs, Transcription Factors and Target Genes in Neuroblastoma

A Focus on Regulatory Networks Linking MicroRNAs, Transcription Factors and Target Genes in Neuroblastoma

Neuroblastoma Heterogeneity, Plasticity, and Emerging Therapies

BET and CDK Inhibition Reveal Differences in the Proliferation Control of Sympathetic Ganglion Neuroblasts and Adrenal Chromaffin Cells

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