FBP2 inhibits sarcoma progression by restraining mitochondrial biogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA566448 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10149775.fastq.gz | Fastqsanger.gz | |||
| SRR10149776.fastq.gz | Fastqsanger.gz | |||
| SRR10149777.fastq.gz | Fastqsanger.gz | |||
| SRR10149778.fastq.gz | Fastqsanger.gz | |||
| SRR10149779.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 9 |
Similar Datasets
Project description:We show that expression of the gluconeogenic isozyme fructose-1,6-bisphosphatase 2 (FBP2) is silenced in a broad spectrum of soft tissue sarcoma (STS) subtypes, revealing an apparent common metabolic feature shared by diverse STS. Enforced FBP2 expression inhibits STS cell and tumor growth through two distinct mechanisms. First, cytosolic FBP2 antagonizes elevated glycolysis associated with the “Warburg effect”, thereby inhibiting sarcoma cell proliferation. Second, nuclear-localized FBP2 restrains mitochondrial biogenesis and respiration in a catalytic activity-independent manner by inhibiting the expression of nuclear respiratory factor (NRF1) and mitochondrial transcription factor A (TFAM). Specifically, nuclear FBP2 colocalizes with the c-Myc transcription factor at the TFAM locus and represses c-Myc-dependent TFAM expression. This unique dual function of FBP2 provides a rationale for its selective suppression in STS, identifying a potential metabolic vulnerability and possible therapeutic target. This study aims to globally compare the transcriptomes from control or FBP2-expressing LPS246 cells. Total RNA was isolated from 5 sets of control cells and 5 sets of FBP2-expressing cells using RNeasy Mini Kit (Qiagen). Low-throughput library prep using Illumina truSeq stranded mRNA kit. The sequencing were performed on Illumina Platform 100SR, with 312 million raw reads/sample.
2019-09-20 | GSE137755 | GEO
Project description:The remarkable cellular and genetic heterogeneity of soft tissue sarcomas (STSs) limits the clinical benefit of targeted therapies. Here, we show that expression of the gluconeogenic isozyme fructose-1,6-bisphosphatase 2 (FBP2) is silenced in a broad spectrum of sarcoma subtypes, revealing an apparent common metabolic feature shared by diverse STSs. Enforced FBP2 expression inhibits sarcoma cell and tumor growth through two distinct mechanisms. First, cytosolic FBP2 antagonizes elevated glycolysis associated with the "Warburg effect," thereby inhibiting sarcoma cell proliferation. Second, nuclear-localized FBP2 restrains mitochondrial biogenesis and respiration in a catalytic-activity-independent manner by inhibiting the expression of nuclear respiratory factor and mitochondrial transcription factor A (TFAM). Specifically, nuclear FBP2 colocalizes with the c-Myc transcription factor at the TFAM locus and represses c-Myc-dependent TFAM expression. This unique dual function of FBP2 provides a rationale for its selective suppression in STSs, identifying a potential metabolic vulnerability of this malignancy and possible therapeutic target.
| S-EPMC6949384 | biostudies-literature
Project description:Apigenin inhibits tumor angiogenesis by suppressing microvesicle biogenesis
| PRJNA1055490 | ENA
Project description:Apigenin regulates multiple pathways related to microvesicle biogenesis without affecting the expression of small Rho GTPase activator guanine nucleotide exchange factors (GEFs). However, apigenin can primarily targets ARHGEF1 protein, a GEF of the small GTPases, thereby inhibiting the activity of small G proteins such as Cdc42, which is essential in regulating the signaling for the release of microvesicles from tumor cells. Targeting ARHGEF1, apigenin effectively prevents tumor cells from releasing microvesicles. This, in turn, inhibits tumor angiogenesis related to VEGF90K transport on microvesicles, ultimately impeding tumor progression.
2024-07-22 | GSE251817 | GEO
Project description:Demethylzeylasteral inhibits oxidative phosphorylation complex biogenesis by targeting LRPPRC in lung cancer
| PRJNA1170897 | ENA
Project description:Caloric restriction (CR) without malnutrition appears to mitigate many detrimental effects of aging, in particular the age-related decline in skeletal muscle mitochondrial function. Although the mechanisms responsible for this protective effect remain unclear, CR is commonly believed to increase mitochondrial biogenesis; a concept that is now demanding closer scrutiny. Here we show that lifelong CR in mice prevents age-related loss of mitochondrial function, measured in isolated mitochondria and permeabilized muscle fibers. We find that these beneficial effects of CR occur without increasing mitochondrial abundance. Furthermore, whole-genome expression profiling and large-scale proteomic surveys revealed expression patterns inconsistent with increased mitochondrial biogenesis. These observations, combined with lower protein synthesis rates support an alternative hypothesis that CR preserves mitochondrial function not by increasing mitochondrial biogenesis, but rather by decreasing mitochondrial oxidant emission, increasing antioxidant scavenging, thereby minimizing oxidative damage to cellular components. Cross-sectional comparison of skeletal muscle from young (8mo), old (24mo) and old caloric restricted mice, obtained from the colony maintained on behalf of the National Institute on Aging.
2013-01-01 | E-GEOD-36285 | biostudies-arrayexpress
Project description:Androgen receptor (AR) is expressed in both the prostate epithelium and the prostate stroma and plays diverse roles in prostate physiology. Although low expression of stromal AR is clinically associated with advanced cancer stage and worse outcome, whether stromal AR inhibits or promotes prostate cancer progression remains controversial. Here, we specifically delete AR in smooth muscle cells of the adult mouse prostate under two tumorigenic conditions, namely, the Hi-Myc genetic model and the T + E2 hormonal carcinogenesis model. Histology analyses show that stromal AR deletion exacerbates tumor progression phenotypes in both models. Furthermore, single-cell analyses of the tumor samples reveal that secretory luminal cells are the cell population particularly affected by stromal AR deletion, as they transition to a cellular state of potentiated PI3K-mTORC1 activities. Our results suggest that stromal AR normally inhibits prostate cancer progression by restraining secretory luminal cells and imply possible unintended negative effects of androgen deprivation therapy.
| S-EPMC9175887 | biostudies-literature
Project description:SIRT3 is a NAD+-dependent mitochondrial protein deacetylase participating in the regulation of central metabolism and mitochondrial proteostasis. SIRT3 is downregulated in clear cell renal cell carcinoma (ccRCC), a main type of renal cancers, but the function of SIRT3 in tumorigenesis and development of ccRCC remains unknown. In this study, we established a SIRT3 overexpressed cell line to explore the changes of proteomics and metabolomics regulated by SIRT3 expression. Both the results of quantitative proteomics, metabolomics and acetylome showed overexpression of SIRT3 increased mitochondrial biogenesis and reversed the mitochondrial dysfunctions in ccRCC. We found SIRT3 could increase the activity of TFAM through modulation of TFAM transcription, degradation and acetylation level. The acetylation of TFAM K154 decreased while TFAM protein expression increased after SIRT3 overexpression. Further study revealed that SIRT3 could bind with TFAM, and decrease the acetylation of TFAM, promoting TFAM activity in mitochondrial biogenesis. Overall, our results present a new mechanism of SIRT3 in regulating mitochondrial functions, and the downregulation of SIRT3 in ccRCC lowers the activity of TFAM, subsequently inhibits the transcription of mitochondrial genes and mitochondrial biogenesis.
2018-08-14 | PXD009110 | Pride
Project description:Cells respond to mitochondrial energetic stress with rapid activation of the AMP-activated protein kinase (AMPK), which acutely inhibits anabolism and stimulates catabolism. AMPK also induces sustained transcriptional reprogramming of metabolism. The TFEB transcription factor is a major effector of AMPK signals, inducing lysosome genes following energetic stress. Yet the molecular mechanism underlying how AMPK activates TFEB remains unresolved. We demonstrate here that AMPK directly phosphorylates five conserved serine residues in FNIP1, which suppresses the function of the FLCN/FNIP1 RagC GAP complex, in turn controlling TFEB lysosomal localization. We demonstrate that FNIP1 phosphorylation is required for AMPK to induce nuclear translocation of TFEB, which is fully separable from AMPK control of canonical mTORC1 signaling. Using a non-phosphorylatable allele of FNIP1, we show that in parallel to lysosomal biogenesis, AMPK induces mitochondrial biogenesis via TFEB-dependent induction of PGC1a mRNA. This signaling from mitochondrial stress is also independent of amino-acid control of the Rags and TFEB, which still proceed normally in cells bearing the AMPK-non phosphorylatable allele of FNIP1. Taken together, mitochondrial energetic stress triggers AMPK/FNIP1-dependent TFEB nuclear translocation, inducing transcriptional waves of lysosomal and mitochondrial biogenesis.
2023-05-08 | GSE218827 | GEO
Project description:Microarray time-course of mouse myotubes transduced with the transcriptional co-activator PGC-1alpha, which is known to induce mitochondrial biogenesis in muscle cells. Keywords: time course
2006-04-03 | GSE4330 | GEO