Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuronal mimicry mechanisms promote the growth small-cell lung cancer in the brain

ABSTRACT: Small cell lung cancer (SCLC) is a fatal form of cancer that frequently metastasizes to the brain. Here we investigated the mechanisms allowing SCLC cells to grow in the unique brain microenvironment. We found that neuronal programs upregulated in SCLC cells during tumor progression and upon growth in the brain are critical for SCLC growth in the brain. Mechanistically, the presence of SCLC cells in the brain re-activates astrocytes, which in turn promote the survival of SCLC cells by secreting neuronal pro-survival factors such as SERPINE1. We also identified Reelin, a molecule produced by developing neurons to recruit astrocytes, as a molecule secreted by SCLC cells to recruit astrocytes to the tumor site and promote SCLC growth in the brain. Thus, SCLC cells co-opt mechanisms normally at play between astrocytes and neurons to promote SCLC growth in the brain. Targeting such developmental neuronal programs may help treat brain metastases.

ORGANISM(S): Mus musculus

PROVIDER: GSE179032 | GEO | 2023/06/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Neuronal mimicry mechanisms promote the growth of small-cell lung cancer in the brain [human astrocytes RNA-seq]

Project description:Small cell lung cancer (SCLC) is a fatal form of cancer that frequently metastasizes to the brain. Here we investigated the mechanisms allowing SCLC cells to grow in the unique brain microenvironment. We found that neuronal programs upregulated in SCLC cells during tumor progression and upon growth in the brain are critical for SCLC growth in the brain. Mechanistically, the presence of SCLC cells in the brain re-activates astrocytes, which in turn promote the survival of SCLC cells by secreting neuronal pro-survival factors such as SERPINE1. We also identified Reelin, a molecule produced by developing neurons to recruit astrocytes, as a molecule secreted by SCLC cells to recruit astrocytes to the tumor site and promote SCLC growth in the brain. Thus, SCLC cells co-opt mechanisms normally at play between astrocytes and neurons to promote SCLC growth in the brain. Targeting such developmental neuronal programs may help treat brain metastases.

2023-08-09 | GSE178738 | GEO

Neuronal mimicry mechanisms promote the growth of small-cell lung cancer in the brain [human SCLC cell RNA seq]

2023-08-09 | GSE178736 | GEO

An ecosystem mimicking brain development promotes metastatic growth of SCLC in the brain

2023-08-09 | GSE202233 | GEO

Neuronal mimicry mechanisms promote the growth of small-cell lung cancer in the brain [TA and CA RNA-seq]

2023-08-09 | GSE178732 | GEO

Wild type vs. Nova2 KO mouse E14.5 cortex RNA

Project description:To assess the requirement of Nova2 for alternative processing of RNA in the developping brain. Neuronal migration leads to a highly organized laminar structure in the mammalian brain and its mis-regulation causes lissencephaly, behavioral and cognitive defects. Reelin signaling, mediated in part by a key adaptor, disabled-1 (Dab1), plays a critical but incompletely understood role in this process. We found that the neuron-specific RNA binding protein Nova2 regulates neuronal migration in late-generated cortical and Purkinje neurons. An unbiased HITS-CLIP and exon junction array search for Nova-dependent RNAs at E14.5 focused on components of the reelin pathway revealed only one candidate—an alternatively spliced isoform of Dab1 (Dab1.7bc). In utero electroporation demonstrated that Dab1.7bc was sufficient to induce neuronal migration defects in wild-type mice and exacerbate defects when Dab1 levels were reduced, while Dab1 overexpression mitigates defects in Nova2-null mice. Thus Nova2 regulates an RNA switch controlling the ability of Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new links between splicing regulation, brain disease and development. Keywords: Comparative analysis RNA from the cortex of 3 wild type and 3 Nova2 KO E14.5 cortex. One array per biological replicate.

2010-07-07 | E-GEOD-22758 | biostudies-arrayexpress

Wild type vs. Nova2 KO mouse E14.5 cortex RNA

2010-07-07 | GSE22758 | GEO

Disease-relevant upregulation of P2Y1 receptor in astrocytes enhances neuronal excitability via IGFBP2

Project description:Reactive astrocytes play a pivotal role in the pathogenesis of neurological diseases; however, their functional phenotype and the downstream molecules by which they modify disease pathogenesis remain unclear. Here, we genetically increase P2Y1 receptor (P2Y1R) expression, which is upregulated in reactive astrocytes in several neurological diseases, in astrocytes of male mice to explore its function and the downstream molecule. This astrocyte-specific P2Y1R overexpression causes neuronal hyperexcitability by increasing both astrocytic and neuronal Ca2+ signals. We identify insulin-like growth factor-binding protein 2 (IGFBP2) as a downstream molecule of P2Y1R in astrocytes; IGFBP2 acts as an excitatory signal to cause neuronal excitation. In neurological disease models of epilepsy and stroke, reactive astrocytes upregulate P2Y1R and increase IGFBP2. The present findings identify a mechanism underlying astrocyte-driven neuronal hyperexcitability, which is likely to be shared by several neurological disorders, providing insights that might be relevant for intervention in diverse neurological disorders.

2024-05-17 | GSE242450 | GEO