Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LACTB inhibits lipid synthesis to suppress glioma growth by promoting Hsc70-mediated ERBB3 degradation

ABSTRACT: Abnormal lipid metabolism is a hallmark of tumor and represents an anti-cancer strategy. β-lactamase like protein (LACTB) is a novel tumor suppressor, but the biological function and the involved mechanism in glioma remain unclear. Here, we show that LACTB overexpression suppresses glioma growth while LACTB knockdown shows the opposite effect. By RNA-sequencing and untargeted lipidomics analysis, we find that LACTB overexpression inhibits the lipid synthesis of glioma cells. Mechanistically, LACTB downregulates ERBB3 and inhibits PI3K/AKT/mTOR signaling, which restrains the lipogenesis of tumor cells. We further uncover that LACTB overexpression decreases the protein stability of ERBB3 by lysosomal degradation. LACTB promotes the interaction of ERBB3 and Hsc70 to facilitate ERBB3 degradation in lysosome. Finally, we show that targeting LACTB/ERBB3 axis significantly suppresses glioma growth in the mouse model. Therefore, our study reveals the antitumoral role of LACTB in glioma and the LACTB/ERBB3 axis represents a potential new therapeutic target for this tumor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288782 | GEO | 2026/02/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

LACTB inhibits lipid synthesis to suppress glioma growth by promoting Hsc70-mediated ERBB3 degradation

Project description:LACTB inhibits lipid synthesis to suppress glioma growth by promoting Hsc70-mediated ERBB3 degradation

| PRJNA1219396 | ENA

NRG1/ERBB3 signaling in melanocyte Melan-Ink4a cells

Project description:Neuregulin (NRG) signaling through the receptor tyrosine kinase, ERBB3, is required for embryonic development, and dysregulated signaling has been associated with cancer progression. Here, we show that NRG1/ERBB3 signaling inhibits melanocyte (MC) maturation and promotes undifferentiated, migratory and proliferative cellular characteristics. Embryonic analyses demonstrated that initial MC specification and distribution were not dependent on ERBB3 signaling. However NRG1/ERBB3 signaling was both necessary and sufficient to inhibit differentiation of later stages of MC development in culture. Analysis of tissue arrays of human melanoma samples suggests that ERBB3 signaling may also contribute to metastatic progression of melanoma as ERBB3 was phosphorylated in primary tumors compared with nevi or metastatic lesions. Neuregulin 1-treated MCs demonstrated increased proliferation and invasion and altered morphology concomitant with decreased levels of differentiation genes, increased levels of proliferation genes and altered levels of melanoma progression and metastases genes. ERBB3 activation in primary melanomas suggests that NRG1/ERBB3 signaling may contribute to the progression of melanoma from benign nevi to malignancies. We propose that targeting ERBB3 activation and downstream genes identified in this study may provide novel therapeutic interventions for malignant melanoma. Gene expression changes are compared between Melan-Ink4a cells stimulated with NRG1-b1 (NRG1) for 21 days and NRG1 untreated Melan-INK4a cells in triplicate using Affymetrix Mouse GeneChip 1.0 ST chip .

2010-05-07 | E-GEOD-21463 | biostudies-arrayexpress

NRG1/ERBB3 signaling in melanocyte Melan-Ink4a cells

2010-04-26 | GSE21463 | GEO

Targeted ErbB3 loss in mammary organoids harvested from ErbB3 DOX-KO mice +/- DOX treatment

2012-01-04 | GSE32129 | GEO

Targeted ErbB3 loss in mammary organoids harvested from ErbB3 DOX-KO mice +/- DOX treatment

Project description:Mammary organoids harvested from ErbB3 DOX-KO mice, which utilize MMTV-Cre transgene expression in the LE to cause genomic recombination at floxed ErbB3 alleles in ErbB3FL/FL were cultured in the presence or absence of doxycycline to induce ErbB3 loss. The gene expression shift following DOX-induced ErbB3 loss in the 3D organoids was examined by microarray. Gene expression patterns were interrogated in mammary organoids from ErbB3 inducible-knockout mice cultured in the presence of absence of doxycycline. Three biological replicates of the experiment were performed, resulting in a total of 6 samples (3 treatment, 3 control).

2012-01-04 | E-GEOD-32129 | biostudies-arrayexpress

As an unfavorable prognostic factor, LACTB promotes metastasis of nasopharyngeal carcinoma via activation of ERBB3/EGFR-ERK signaling

Project description:Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelium and has the highest metastatic rate among head and neck cancers, NPC metastasis has become the main cause of treatment failure. The molecular basis regulating NPC metastasis remains obscure. Here we discovered a gene named LACTB Highly expressed in NPC tissues and aimed to investigate its role and regulatory mechanism in the metastasis of NPC.LACTB was found to promote NPC cellular motility in vitro and metastasis in vivo via the activation of the ERBB3/EGFR-ERK pathway on a histone H3 depending manner. Also, the elevated expression of LACTB in the primary NPC correlated with patient poor survival, indicating LACTB as a potential prognostic predictor and an anti-metastasis therapeutic target.

2020-05-19 | GSE150761 | GEO

Quantitative phosphoproteomics analysis of ERBB3/ERBB4 signaling

Project description:The four members of the epidermal growth factor receptor (EGFR/ERBB) family form homo- and heterodimers which mediate ligand-specific regulation of many key cellular processes in normal and cancer tissues. While signaling through the EGFR has been extensively studied on the molecular level, signal transduction through ERBB3/ERBB4 heterodimers is less well understood. Here, we generated isogenic mouse Ba/F3 cells that express full-length and functional membrane-integrated ERBB3 and ERBB4 or ERBB4 alone, to serve as a defined cellular model for biological and phosphoproteomics analysis of ERBB3/ERBB4 signaling. ERBB3 co-expression significantly enhanced Ba/F3 cell proliferation upon neuregulin-1 (NRG1) treatment. For comprehensive signaling studies we performed quantitative mass spectrometry (MS) experiments to compare the basal ERBB3/ERBB4 cell phosphoproteome to NRG1 treatment of ERBB3/ERBB4 and ERBB4 cells. We employed a workflow comprising differential isotope labeling with mTRAQ reagents followed by chromatographic peptide separation and final phosphopeptide enrichment prior to MS analysis. Overall, we identified 9686 phosphorylation sites which could be confidently localized to specific residues. Statistical analysis of three replicate experiments revealed 492 phosphorylation sites which were significantly changed in NRG1-treated ERBB3/ERBB4 cells. Bioinformatics data analysis recapitulated regulation of mitogen-activated protein kinase and Akt pathways, but also indicated signaling links to cytoskeletal functions and nuclear biology. Comparative assessment of NRG1-stimulated ERBB4 Ba/F3 cells indicated that ERBB3 did not trigger defined signaling pathways but more broadly enhanced phosphoproteome regulation in cells expressing both receptors. In conclusion, our data provide the first global picture of ERBB3/ERBB4 signaling and provide numerous potential starting points for further mechanistic studies

2016-01-15 | PXD002665 | Pride

Conditional loss of ErbB3 delays mammary gland hyperplasias induced by mutant PIK3CA but does not affect mammary tumor latency, gene expression or signaling

Project description:Mutations in PIK3CA, the gene encoding the p110α subunit of PI3K, induce transformation of mammary epithelial cells (MEC). Studies suggest the transforming action of mutant PIK3CA requires binding to activated receptor tyrosine kinases or adaptors. We examined in transgenic mice if ErbB3, a powerful activator of PI3K, is required for mutant PIK3CA-mediated MEC transformation. ErbB3 loss delayed PIK3CAH1047R-dependent mammary gland hyperplasia, but tumor latency, gene expression and markers of PI3K signaling were unaffected. In ErbB3-deficient tumors, mutant PI3K remained associated with other tyrosine phosphorylated adaptors, potentially explaining the dispensability of ErbB3 for tumorigenicity and PI3K activity. Combined inhibition of ErbB RTKs and PI3K with lapatinib and the p110α inhibitor BYL719, respectively, reduced PIK3CAH1047R-dependent tumor growth and PI3K signaling more potently than the p110α inhibitor alone. In human breast cancer cells harboring PIK3CAH1047R, the combination with BYL719 and an ErbB3 inhibitor synergistically inhibited tumor growth and P-Akt. These data suggest that basal tumor growth and PI3K signaling do not depend on ErbB RTKs in PIK3CAH1047R-expressing tumors. However, upon inhibition of p110α, these receptors limit the action of PI3K inhibitors potentially explaining the more potent effect of the combination against PI3K-mutant cancers. reference x sample

2013-06-20 | E-GEOD-43037 | biostudies-arrayexpress

Conditional loss of ErbB3 delays mammary gland hyperplasias induced by mutant PIK3CA but does not affect mammary tumor latency, gene expression or signaling

2013-06-20 | GSE43037 | GEO

Stromal Erbb3 shapes uterine gland morphogenesis

Project description:Stromal Erbb3 shapes uterine gland morphogenesis

| PRJNA1334398 | ENA