Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Endothelial-to-mesenchymal transition in tumor mesenchymal stem cells elicits pro-tumorigenic IL-11+ cancer-associated myofibroblasts [TGFB_bulkRNAseq]

ABSTRACT: Tumor mesenchymal stem cells (TMSCs) orchestrate tumor microenvironment (TME) transformation via their ability to transdifferentiate. Metastatic solid tumors often feature neural crest-like/mesenchymal phenotypes characterized by high expression levels of TGFβ-dependent epithelial-to-mesenchymal transition (EMT) and EMT-like programs. Specifically, EMT-like endothelial-to-mesenchymal (EndMT) programs are responsible for the differentiation of TMSCs towards cancer-associated fibroblasts (CAFs). CAFs dictate tumor progression, invasiveness, and immune evasion. Exploring the molecular determinants of CAFs generation and pathobiology is thus of paramount importance to improve therapy response. The in vitro responses of patient-derived TMSCs were investigated upon recapitulating TGFβ-driven EMT-like TME traits. The resulting myofibroblastic CAFs (myCAFs) originated from TMSCs via EndMT were characterized by enhanced Interleukin-11 (IL11) expression and secretion. We propose IL11+ myCAFs as a driver of the tumor-stromal crosstalk responsible for the pro-tumorigenic, mesenchymal, angiogenic, and immunosuppressive TME transformation in metastatic melanoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE338554 | GEO | 2026/07/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Endothelial-to-mesenchymal transition in tumor mesenchymal stem cells elicits pro-tumorigenic IL-11+ cancer-associated myofibroblasts [TGFB_scRNAseq]

Project description:Tumor mesenchymal stem cells (TMSCs) orchestrate tumor microenvironment (TME) transformation via their ability to transdifferentiate. Metastatic solid tumors often feature neural crest-like/mesenchymal phenotypes characterized by high expression levels of TGFβ-dependent epithelial-to-mesenchymal transition (EMT) and EMT-like programs. Specifically, EMT-like endothelial-to-mesenchymal (EndMT) programs are responsible for the differentiation of TMSCs towards cancer-associated fibroblasts (CAFs). CAFs dictate tumor progression, invasiveness, and immune evasion. Exploring the molecular determinants of CAFs generation and pathobiology is thus of paramount importance to improve therapy response. The in vitro responses of patient-derived TMSCs were investigated upon recapitulating TGFβ-driven EMT-like TME traits. The resulting myofibroblastic CAFs (myCAFs) originated from TMSCs via EndMT were characterized by enhanced Interleukin-11 (IL11) expression and secretion. We propose IL11+ myCAFs as a driver of the tumor-stromal crosstalk responsible for the pro-tumorigenic, mesenchymal, angiogenic, and immunosuppressive TME transformation in metastatic melanoma.

2026-07-18 | GSE338555 | GEO

Endothelial-to-mesenchymal transition in tumor mesenchymal stem cells elicits pro-tumorigenic IL-11+ cancer-associated myofibroblasts [Full_Low_Serum]

2026-07-18 | GSE338553 | GEO

Tumor-produced and aging-associated oncometabolite, methylmalonic acid, promotes cancer-associated fibroblast activation to drive metastatic progression

Project description:The systemic metabolic shifts that occur during aging and the local metabolic alterations of a tumor, its stroma and their communication cooperate to establish a unique tumor microenvironment (TME) that fosters cancer progression. Here, we show that methylmalonic acid (MMA), an aging-increased oncometabolite that is also produced by aggressive cancer cells, activates fibroblasts in the TME and stimulates the release of extracellular vesicles (EVs) that drive cancer progression, drug resistance and metastasis. The cancer-associated fibroblast (CAF)-released EV cargo is modified as a result of reactive oxygen species (ROS) generation and activation of the canonical and noncanonical TGFβ signaling pathways in CAFs. EV-associated IL-6 functions as a stroma-tumor messenger that activates the JAK/STAT3 and TGFβ signaling pathways in tumor cells and promote an epithelial-to-mesenchymal transition (EMT) and drug resistance in vitro, and metastatic progression in vivo. Our findings reveal the role of MMA in the activation of CAFs to drive metastatic reprogramming, unveiling multiple potential therapeutic avenues to target MMA at the nexus of aging, the tumor microenvironment and metastasis.

2022-10-04 | GSE190929 | GEO

Regan2022 - Mechanosensitive EMT model with autocrine TGFbeta signaling

Project description:This model is an expansion of the Regan2022 - Mechanosensitive EMT model (MODEL2208050001); it includes a TGFβ signaling module and autocrine signaling in mesenchymal cells. The expanded 150-node (630 link) modular model undergoes EMT triggered by biomechanical and growth signaling crosstalk, or by TGFβ. As its predecessor, this model also reproduces the ability of the core EMT transcriptional network to maintain distinct epithelial, hybrid E/M and mesenchymal states, as well as EMT driven by mitogens such as EGF on stiff ECM. We also reproduce the observed lack of stepwise MET, in that our model's dynamics does not pass through the hybrid E/M state during MET. We show that in the absence of strong autocrine signals such as TGFβ (not included in this version), cells cannot maintain their mesenchymal state in the absence of mitogens, on softer matrices, or at high cell density. In contrast, potent autocrine signaling can stabilize the mesenchymal state in all but very dense monolayers on soft ECM. This expanded model also reproduces the inhibitory effects of TGFβ on proliferation and anoikis resistance in mesenchymal cells, as well as its ability to trigger apoptosis on soft ECM vs. EMT on stiff matrices. The model offers several experimentally testable predictions related to the effect of neighbors on partial vs. full EMT, the tug of war between mitosis and the maintenance of migratory hybrid E/M states, as well as cell cycle defects in dynamic, heterogeneous populations of epithelial, hybrid E/M and mesenchymal cells.

2023-12-13 | MODEL2208050002 | BioModels

A Wnt-induced phenotypic switch in cancer-associated fibroblasts inhibits EMT in colorectal cancer

Project description:Tumor progression is recognized as a result of an evolving crosstalk between tumor cells and their surrounding non-transformed stroma. Although Wnt signaling has been intensively studied in colorectal cancer (CRC), it remains unclear whether activity in the tumor-associated stroma contributes to malignancy. To specifically interfere with stromal signals, we generated Wnt-independent tumor organoids that secrete the Wnt antagonist Sfrp1. Upon subcutaneous transplantation into immuno-competent as well as -deficient mice, we observed strong reduction of tumor growth. Histological and transcriptomic analyses revealed that Sfrp1 induces an EMT (epithelial-mesenchymal transition) phenotype in tumor cells without affecting tumor-intrinsic Wnt signaling, suggesting involvement of non-immune stromal cells. Indeed, blockage of canonical signaling using Sfrp1, Dkk1, or fibroblast-specific genetic ablation of β-catenin strongly decreased the number of cancer-associated myofibroblasts (myCAFs). Interestingly, we found that the Wnt activity in CAFs is linked with distinct subtypes, where low and high levels induce an inflammatory-like CAF (iCAF) subtype or contractile myCAFs, respectively. Co-culture of tumor organoids with iCAFs resulted in massive upregulation of EMT markers, while myCAFs reverted this phenotype. In summary, we show that tumor growth and malignancy are differentially regulated via district fibroblast subtypes under the influence of juxtacrine Wnt signals.

2020-10-15 | GSE155364 | GEO

Secretomes from non-small cell lung cancer cells induce endothelial plasticity through a partial endothelial-to-mesenchymal transition

Project description:The tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) is highly heterogeneous and is involved in tumorigenesis and resistance to therapy. Among the cells of the TME, endothelial cells are associated with the latter processes through endothelial-to-mesenchymal transition (EndMT). During EndMT, endothelial cells (ECs) progressively lose their endothelial phenotype in favor of a mesenchymal phenotype, which favors the production of cancer-associated fibroblasts. Our study aimed to investigate the consequences of exposure to different lung tumor secretomes on EC phenotype and plasticity. Conditioned media (CM) were prepared from the tumor cell lines A549, H1755, H23, H1437 and H1975. Proliferation and migration of endothelial cells treated with these CMs were assessed by Cyquant® and Incucyte® technologies, respectively. The angiogenic capacity of ECs was assessed by following tubulogenesis on Matrigel®. Phenotypic changes in treated ECs were detected by flow cytometry. Morphological analysis of actin fibers was performed by immunohistochemistry, while proteomic analysis by mass spectrometry was used to identify the protein content of secretomes. A change of the endothelial phenotype was found when HUVECs were treated with different CMs. This phenotypic change was associated with a morphological change, an increase in both stress fiber expression and spontaneous migration. Furthermore, an increase in mesenchymal markers (±-SMA and CD44) confirmed the phenotypic changes. However, the secretomes did not modify the rate of double-labelled cells (vWF+/-SMA+ or CD31+/CD44+). Proteomic analysis identified potential targets involved in the EndMT with therapeutic relevance. Taken together, these data suggest that CMs are capable of inducing partial EndMT.

2025-04-24 | PXD054295 | Pride

Differential protein secretome induced by TNF-alpha

Project description:Endothelial-mesenchymal-transition (EndMT) is an important source of cancer-associated fibroblasts (CAFs), which are known to facilitate tumor progression. We have previously shown that EndMT is present in pancreatic tumors and that deficiency of the Tie1 receptor induces EndMT in human endothelial cells. Pancreatic tumors are characterized by the presence of tumor necrosis factor-α (TNF-α). We now show that TNF-α strongly induces human endothelial cells to undergo EndMT. In order to know the secretory feature of cells which undergo EndMT by TNF-α, we conducted a comparative analysis of HMVEC secretome treated or not for 24h and 48h with TNF-α. Secretome study shows that cells treated with TNF-α have an important fibroblast-like secretory capacity, and a proinflamatory signature. Moreover, Ingenuity Pathway Analysis (IPA) shows that pathways implicated in migration, inflammation and fibrosis are predicted to be activated and that necrosis and apoptosis pathways are inhibited. Accordingly cell survival, viability and cycle progression are activated. We show that TNF-α- treated cells secrete proteins related to 16 protumoral pathways, confirming their fibroblastic characteristic. Finally, among the predicted upstream regulators activated, IPA analysis shows that, TNFSF12 and its receptor are present at hight levels in PDAC patients. Altogether these results show the fibroblastic characteristic of treated cells and demonstrate that TNF-α induces CAFs.

2021-09-08 | PXD014488 | Pride

Regan2022 - Mechanosensitive EMT model

Project description:This file contains a 136-node modular Boolean network model of EMT triggered by biomechanical and growth signaling crosstalk, linked to a published network of epithelial contact inhibition, proliferation, and apoptosis (MODEL2006170001). This model reproduces the ability of the core EMT transcriptional network to maintain distinct epithelial, hybrid E/M and mesenchymal states, as well as EMT driven by mitogens such as EGF on stiff ECM. We also reproduce the observed lack of stepwise MET, in that our model's dynamics does not pass through the hybrid E/M state during MET. We show that in the absence of strong autocrine signals such as TGFβ (not included in this version), cells cannot maintain their mesenchymal state in the absence of mitogens, on softer matrices, or at high cell density.

2023-12-13 | MODEL2208050001 | BioModels

Mesothelioma-associated fibroblasts enhance proliferation and migration of malignant pleural mesothelioma cells via Met/PI3K and WNT signaling but do not protect against cisplatin

Project description:Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis. Unlike many other cancers, MPM is mostly characterized by inactivation of tumor suppressor genes. Its highly malignant nature in absence of tumor driving oncogene mutations indicates an extrinsic supply of stimulating signals by cells of the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are an abundant cell type of the TME and have been shown to drive the progression of several cancer types. The aim of the current study was to isolate and characterize patient-derived mesothelioma-associated fibroblasts (Meso-CAFs), and evaluate their impact on MPM cells.

2022-12-31 | E-MTAB-12179 | biostudies-arrayexpress

Glutamine deficiency drives transforming growth factor-β signaling activation that gives rise to myofibroblastic carcinoma-associated fibroblasts

Project description:Tumor-promoting carcinoma-associated fibroblasts (CAFs), abundant in the mammary tumor microenvironment (TME), maintain transforming growth factor-β (TGF-β)-Smad2/3 signaling activation and the myofibroblastic state, the hallmark of activated fibroblasts. How myofibroblastic CAFs (myCAFs) arise in the TME and which epigenetic and metabolic alterations underlie activated fibroblastic phenotypes remain, however, poorly understood. We herein show global histone deacetylation in myCAFs present in tumors to be significantly associated with poorer outcomes in breast cancer patients. As the TME is subject to glutamine (Gln) deficiency, human mammary fibroblasts (HMFs) were cultured in Gln-starved medium. Global histone deacetylation and TGF-β-Smad2/3 signaling activation are induced in these cells, largely mediated by class I histone deacetylase (HDAC) activity. Additionally, mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signaling is attenuated in Gln-starved HMFs, and mTORC1 inhibition in Gln-supplemented HMFs with rapamycin treatment boosts TGF-β-Smad2/3 signaling activation. These data indicate that mTORC1 suppression mediates TGF-β-Smad2/3 signaling activation in Gln-starved HMFs. Global histone deacetylation, class I HDAC activation, and mTORC1 suppression are also observed in cultured human breast CAFs. Class I HDAC inhibition or mTORC1 activation by high-dose Gln supplementation significantly attenuates TGF-β-Smad2/3 signaling and the myofibroblastic state in these cells. These data indicate class I HDAC activation and mTORC1 suppression to be required for maintenance of myCAF traits. Taken together, these findings indicate that Gln starvation triggers TGF-β signaling activation in HMFs through class I HDAC activity and mTORC1 suppression, presumably inducing myCAF conversion.

2023-11-03 | GSE217046 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data