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Active elimination of intestinal cells drives oncogenic growth in organoids

ABSTRACT: Active elimination of intestinal cells drives oncogenic growth in organoids

PROVIDER: PRJNA734897 | ENA |

REPOSITORIES: ENA

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Active elimination of intestinal cells drives oncogenic growth in organoids

Project description:Competitive cell-interactions play a crucial role in quality control during development and homeostasis. Here we show that cancer cells use such interactions to actively eliminate wild-type intestine cells in enteroid monolayers and organoids. This apoptosis-dependent process boosts proliferation of intestinal cancer cells. The remaining wild-type population activates markers of primitive epithelia and transits to a fetal-like state. Prevention of this cell fate transition avoids elimination of wild-type cells and, importantly, limits the proliferation of cancer cells. JNK signaling is activated in competing cells and is required for cell fate change and elimination of wild-type cells. Thus, cell competition drives growth of cancer cells by active out-competition of wild-type cells through forced cell death and cell fate change in a JNK dependent manner.

2021-07-06 | GSE176027 | GEO

Active elimination of intestinal cells drives oncogenic growth in organoids.

Project description:Competitive cell interactions play a crucial role in quality control during development and homeostasis. Here, we show that cancer cells use such interactions to actively eliminate wild-type intestine cells in enteroid monolayers and organoids. This apoptosis-dependent process boosts proliferation of intestinal cancer cells. The remaining wild-type population activates markers of primitive epithelia and transits to a fetal-like state. Prevention of this cell-state transition avoids elimination of wild-type cells and, importantly, limits the proliferation of cancer cells. Jun N-terminal kinase (JNK) signaling is activated in competing cells and is required for cell-state change and elimination of wild-type cells. Thus, cell competition drives growth of cancer cells by active out-competition of wild-type cells through forced cell death and cell-state change in a JNK-dependent manner.

| S-EPMC8278394 | biostudies-literature

Gene expression changes in oncogenic Kras-containing, Apc-mutated mouse intestinal organoids in the presence or absence of TGF-beta

Project description:We isolated and selected intestinal adenoma organoids from Apc1638N/+ and Apc1638N/+; Kras mice. After the selection procedure, we maintained the cultures with or without TGF-beta for 18h. RNA was isolated to determine the effect of oncogenic Kras on the gene expression changes. Total RNA obtained from Apc1638N/+; Kras organoids were compared to Apc1638N/+ samples in the absence or presence of 3 ng/ml TGF-beta (18h).

2014-04-18 | E-GEOD-35092 | biostudies-arrayexpress

Oncogenic KRAS(G12V) and BRAF(V600E) in intestinal organoids

Project description:Oncogenic KRAS(G12V) and BRAF(V600E) in intestinal organoids

| PRJNA474218 | ENA

Relaxed initiation pausing of ribosomes drives oncogenic translation

Project description:Relaxed initiation pausing of ribosomes drives oncogenic translation

| PRJNA667952 | ENA

METTL1-mediated m7G tRNA modification drives oncogenic transformation

Project description:METTL1-mediated m7G tRNA modification drives oncogenic transformation

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Gene expression changes in oncogenic Kras-containing, Apc-mutated mouse intestinal organoids in the presence or absence of TGF-beta

2014-04-18 | GSE35092 | GEO

Human colon organoids reveal distinct physiologic and oncogenic Wnt responses

Project description:Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed transcriptome and proteome profiling in isogenic human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC.

2019-02-28 | PXD012650 | Pride

Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma

Project description:Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma

| PRJNA615866 | ENA

Lipid Profiling of Mouse Intestinal Organoids for studying APC Mutations

Project description:Inactivating mutations including both germline and somatic mutations in the adenomatous polyposis coli (APC) gene drives most familial and sporadic colorectal cancers. Understanding the metabolic implications of this mutation will aid to establish its wider impact on cellular behaviour and potentially inform clinical decisions. However, to date, alterations in lipid metabolism induced by APC mutations remain unclear. Intestinal organoids have gained widespread popularity in studying colorectal cancer and chemotherapies, because their three-dimensional structure more accurately mimics an in vivo environment. Here, we aimed to investigate intra-cellular lipid disturbances induced by APC gene mutations in intestinal organoids using a reversed-phase ultra-high-performance liquid chromatography mass spectrometry (RP-UHPLC-MS)-based lipid profiling method. Lipids of the organoids grown from either wildtype (WT) or mice with Apc mutations (Lgr5–EGFP-IRES-CreERT2 Apcfl/fl) were extracted and analysed using RP-UHPLC-MS. Concentrations of phospholipids (e.g. PC(16:0/16:0), PC(18:1/20:0), PC(38:0), PC(18:1/22:1)), ceramides (e.g. Cer(d18:0/22:0), Cer(d42:0), Cer(d18:1/24:1)) and hexosylceramide (e.g. HexCer(d18:1/16:0), HexCer(d18:1/22:0)) were higher in Apcfl/fl organoids, whereas levels of sphingomyelins (e.g. SM(d18:1/14:0), SM(d18:1/16:0) ) were lower compared to WT. These observations indicate that cellular metabolism of sphingomyelin was upregulated, resulting in the cellular accumulation of ceramides and production of HexCer due to the absence of Apcfl/fl in the organoids. Our observations demonstrated lipid profiling of organoids and provided an enhanced insight into the effects of the APC mutations on lipid metabolism, making for a valuable addition to screening options of the organoid lipidome.

2021-02-17 | ST001707 | MetabolomicsWorkbench

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