Dataset Information

FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells.

ABSTRACT:

Background

Glioma stem cells (GSCs) are a subpopulation of tumor cells with self-renewal and tumorigenic capabilities in glioblastomas (GBMs). Diffuse infiltration of GSCs facilitates tumor progression and frustrates efforts at effective treatment. Further compounding this situation is the currently limited understanding of what drives GSC invasion. Here we comprehensively evaluated the significance of a novel invasion-related protein, Family with Sequence Similarity 129 Member A (FAM129A), in infiltrative GSCs.

Methods

Western blotting, immunohistochemistry, and gene expression analysis were used to quantify FAM129A in glioma specimens and cancer datasets. Overexpression and knockdown of FAM129A in GSCs were used to investigate its effects on tumor growth and invasion. RNA-seq, qRT-PCR, western blotting, and co-precipitation assays were used to investigate FAM129A signaling mechanisms.

Results

FAM129A is preferentially expressed in invasive frontiers. Targeting FAM129A impairs GSC invasion and self-renewal. Mechanistically, FAM129A acted as a positive regulator of Notch signaling by binding with the Notch1 intracellular domain (NICD1) and preventing its degradation.

Conclusions

FAM129A and NICD1 provide a precise indicator for identifying tumor margins and aiding prognosis. Targeting them may provide a significantly therapeutic strategy for GSCs.

SUBMITTER: Liu G

PROVIDER: S-EPMC10547521 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells.

Liu Guohao G Zhang Po P Chen Sui S Chen Zirong Z Qiu Yanmei Y Peng Peng P Huang Wenda W Cheng Fangling F Zhang Yang Y Li Huan H Xiao Qungen Q Mao Feng F Wang Baofeng B Jiang Xiaobing X Wan Feng F Guo Dongsheng D Yu Xingjiang X

Neuro-oncology 20231001 10

<h4>Background</h4>Glioma stem cells (GSCs) are a subpopulation of tumor cells with self-renewal and tumorigenic capabilities in glioblastomas (GBMs). Diffuse infiltration of GSCs facilitates tumor progression and frustrates efforts at effective treatment. Further compounding this situation is the currently limited understanding of what drives GSC invasion. Here we comprehensively evaluated the significance of a novel invasion-related protein, Family with Sequence Similarity 129 Member A (FAM129 ...[more]

PMID: 37083136

Similar Datasets

Project description:ObjectiveThe Notch family of intermembrane receptors is highly conserved across species and is involved in cell fate and lineage control. Previous in vitro studies have shown that Notch may inhibit adipogenesis. Here we describe the role of Notch in adipose tissue by employing an in vivo murine model which overexpresses Notch in adipose tissue.MethodsAlbino C57BL/6J Rosa(NICD/NICD)::Adipoq-Cre (Ad-NICD) male mice were generated to overexpress the Notch intracellular domain (NICD) specifically in adipocytes. Male Rosa(NICD/NICD) mice were used as controls. Mice were evaluated metabolically at the ages of 1 and 3 months by assessing body weights, serum metabolites, body composition (EchoMRI), glucose tolerance and insulin tolerance. Histological sections of adipose tissue depots as well as of liver were examined. The mRNA expression profile of genes involved in adipogenesis was analyzed by quantitative real-time PCR.ResultsThe Ad-NICD mice were heavier with significantly lower body fat mass compared to the controls. Small amounts of white adipose tissue could be seen in the 1-month old Ad-NICD mice, but was almost absent in the 3-months old mice. The Ad-NICD mice also had higher serum levels of glucose, insulin, triglyceride and non-esterified fatty acids. These differences were more prominent in the older (3-months) than in the younger (1-month) mice. The Ad-NICD mice also showed severe insulin resistance along with a steatotic liver. Gene expression analysis in the adipose tissue depots showed a significant repression of lipogenic (Fasn, Acacb) and adipogenic pathways (C/ebpα, C/ebpβ, Pparγ2, Srebf1).ConclusionsIncreased Notch signaling in adipocytes in mice results in blocked expansion of white adipose tissue which leads to ectopic accumulation of lipids and insulin resistance, thus to a lipodystrophic phenotype. These results suggest that further investigation of the role of Notch signaling in adipocytes could lead to the manipulation of this pathway for therapeutic interventions in metabolic disease.

Dataset Information

FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells.

Background

Methods

Results

Conclusions

Publications

FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells.

Similar Datasets

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