Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Analysis of FBXW7 mutants in colon organoids

ABSTRACT: FBXW7 mutations reduce EGF-dependency and drive CRC tumorigenesis

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Ziliang Ma

LAB HEAD: Wei Wu

PROVIDER: PXD049708 | Pride | 2024-02-20

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20210426_EX3_UM7_wu000024_SA_NS_UbiFPS_1.raw	Raw
	20210426_EX3_UM7_wu000024_SA_NS_UbiFPS_2.raw	Raw
	20210426_EX3_UM7_wu000024_SA_NS_UbiFPS_3.raw	Raw
	20210426_EX3_UM7_wu000024_SA_NS_UbiR505C_1.raw	Raw
	20210426_EX3_UM7_wu000024_SA_NS_UbiR505C_2.raw	Raw

Items per page:

1 - 5 of 21

Similar Datasets

FBXW7

Project description:FBXW7

| PRJNA783287 | ENA

FBXW7

Project description:Purpose: FBXW7 is one of the most frequently mutated tumor suppressors, the deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatic analyses and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multi-drug resistance (MDR), to a bigger extent than well-established MDR-drivers such as ABCB1. Proteomic data from FBXW7-deficient cells and human cancer samples identify the upregulation of mitochondrial function as a hallmark of FBXW7 deficiency, which has been previously linked to an increased resistance to chemotherapy. Accordingly, genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. For instance, targeting mitochondrial translation with the antibiotic Tigecycline efficiently kills FBXW7-deficient cells in vitro and in vivo, by a mechanism that involves activation of the Integrated Stress Response (ISR). Searching for additional drugs that overcome MDR in FBXW7-deficient cells, we found several targeted therapies such as Erlotinib, Dasatinib or Vemurafenib which unexpectedly also activate the ISR. Together, our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance. Methods: This study was performed in 2 groups of DLD1 cells with duplicate samples per group. Both control (Wild Type, WT) and experimental (FBXW7 -/-, KO) were exposed to Tigecycline (10µM). DMSO was used as a control for the treatment. After 24h, the RNA was extracted and the transcriptome was profiled with RNA-Sequencing (RNA-seq) analysis. Results: our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance.

2022-06-09 | GSE189499 | GEO

Effect of FBXW7 loss and concomitant FBXW7-KMT2D loss on mRNA levels

Project description:We assessed the role of the E3 ligase FBXW7 in mature B-cell neoplasms. This experiment assesses the role of the FBXW7-KMT2D axis in regulating gene expression in OPM-1 cells.

2020-04-07 | GSE148131 | GEO

FBXW7 is a defining driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition

Project description:Fbxw7 is a tumor supressor frequently mutated in endometrial cancer. To analyze the signaling pathways that can be altered by Fbxw7 we compared RNA expression in the presence or absence of Fbxw7 in mouse endometrial cancer cells deficient for Fbxw7 and Pten.

2019-11-11 | GSE138490 | GEO

Expression profiling reveals transcriptional regulation by Fbxw7/mTOR pathway in radiation-induced mouse thymic lymphomas

Project description:We used gene transcript profiling to gain a deeper understanding of the role of FBXW7 in tumor development and to determine the influence of mTOR inhibition by rapamycin on tumor transcriptome and biological functions. In comparison to tumors from p53 single heterozygous (p53+/-) mice, we find that tumors from Fbxw7/p53 double heterozygous (Fbxw7+/-p53+/-) mice show significant deregulation of cholesterol metabolic processes independent of rapamycin treatment, while cell cycle related genes were upregulated in tumors from placebo treated Fbxw7+/-p53+/- mice, but not in tumors from rapamycin treated Fbxw7+/-p53+/- mice. On the other hand, tumors from rapamycin treated Fbxw7+/-p53+/- mice were enriched for genes involved in the integrated stress response, an adaptive mechanism to survive in stressful environments. p53+/â and p53+/âFbxw7+/â mice were generated by crossing p53-/- mice with Fbxw7+/- mice. At 5 weeks of age, mice were exposed whole-body to a single dose of 4 Gy X-ray irradiation. Mice were divided randomly into two groups and treated with rapamycin or placebo. RNA was isolated from thymic lymphomas.

2015-10-31 | E-GEOD-71975 | biostudies-arrayexpress

Identification of novel SCF FBXW7 substrates in asynchronous and mitotic cells

Project description:FBXW7 loss-of-function has been implicated in chemoresistance against antimicrotubule drugs. FBXW7 is frequently mutated in human cancers and the identification of FBXW7 substrates, which could be involved in this phenotype, is a major task.

2022-12-02 | PXD035501 | Pride

Targeting mitochondrial translation overcomes multidrug resistance in FBXW7-deficient cells

Project description:FBXW7 is one of the most frequently mutated tumor suppressors, the deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatic analyses and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multi-drug resistance (MDR), to a bigger extent than well-established MDR-drivers such as ABCB1. Proteomic data from FBXW7-deficient cells and human cancer samples identify the upregulation of mitochondrial function as a hallmark of FBXW7 deficiency, which has been previously linked to an increased resistance to chemotherapy. Accordingly, genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. For instance, targeting mitochondrial translation with the antibiotic Tigecycline efficiently kills FBXW7-deficient cells in vitro and in vivo, by a mechanism that involves activation of the Integrated Stress Response (ISR). Searching for additional drugs that overcome MDR in FBXW7-deficient cells, we found several targeted therapies such as Erlotinib, Dasatinib or Vemurafenib which unexpectedly also activate the ISR. Together, our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance.

2022-06-08 | PXD029981 | Pride

FBXW7 coordinates postprandial muscle glucose metabolism and maintenance of skeletal muscle mass

Project description:In this study, we show that muscle-specific inactivation of FBXW7 elicits striking defects in postprandial glucose metabolism and failure to maintain skeletal muscle mass in adult mice. Further, mice lacking FBXW7 exhibited impaired endurance capacity and exacerbated HFD-induced insulin resistance and postprandial hyperglycemia. At the mechanistic level, RNAseq and quantitative proteomic analysis revealed global effects of FBXW7 deficiency on skeletal muscle transcriptome and proteome. This work illustrates a prominent role of FBXW7 in integrating postprandial nutritional signals to coordinate glucose metabolism and muscle mass maintenance.

2024-06-21 | GSE140503 | GEO

Mass spectrometry analysis of proteins interacting with Fbxw7 in T cells

Project description:To elucidate how gut microbiota (GM) downregulated Fbxw7, we treated CD4+ T cells with GM-lysates and pulled down Fbxw7 in the cell lysates. Then, the precipitated proteins were analyzed by mass spectrometry, and eight E3 ligases were revealed to interact with Fbxw7.

2025-04-16 | PXD057140 | Pride

Effect of FBXW7 loss and concomitant FBXW7-KMT2D loss on mRNA levels

Project description:Effect of FBXW7 loss and concomitant FBXW7-KMT2D loss on mRNA levels

| PRJNA623320 | ENA