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Notch1 - WISP1 Axis Determines Tumor-Regulating Role of Melanoma Stromal Fibroblasts

ABSTRACT: Cancer-associated fibroblasts (CAF) are crucial in regulating cancer progression, yet the molecular mechanisms that determine the tumor-regulating function of CAF are poorly understood. Here, we uncover the Notch1 pathway as a molecular determinant that controls the regulatory role of CAF in melanoma growth, invasion and metastasis, and can be manipulated to reprogram and convert CAF to act as tumor suppressors. The Notch1-determined tumor-regulating function is in part mediated by Wnt-induced secreted protein 1 (WISP1). These findings reveal the Notch1âWISP1 axis as a crucial molecular determinant in governing stromal regulation of tumor progression, and establish this axis as a potential therapeutic target Total RNA obtained from MSCD-SF transduced with Cre-GFP/lentivirus in vitro compared to MSCD-SF transduced with GFP/lentivirus. Samples are duplicates.

ORGANISM(S): Mus musculus

SUBMITTER: BIJU ISSAC

PROVIDER: E-GEOD-65316 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Notch1 - WISP1 Axis Determines Tumor-Regulating Role of Melanoma Stromal Fibroblasts

Project description:Cancer-associated fibroblasts (CAF) are crucial in regulating cancer progression, yet the molecular mechanisms that determine the tumor-regulating function of CAF are poorly understood. Here, we uncover the Notch1 pathway as a molecular determinant that controls the regulatory role of CAF in melanoma growth, invasion and metastasis, and can be manipulated to reprogram and convert CAF to act as tumor suppressors. The Notch1-determined tumor-regulating function is in part mediated by Wnt-induced secreted protein 1 (WISP1). These findings reveal the Notch1—WISP1 axis as a crucial molecular determinant in governing stromal regulation of tumor progression, and establish this axis as a potential therapeutic target

2016-05-29 | GSE65316 | GEO

Mus musculus

Project description:Notch1 - WISP1 Axis Determines Tumor-Regulating Role of Melanoma Stromal Fibroblasts

| PRJNA273661 | ENA

Effect of TGFb1 treatment and WISP1 overexpression on 4T1 breast cancer cells

Project description:This study set out to identify TGFb1 transcriptional targets in breast cancer cells. 4T1 breast cancer cells were treated with TGFb1 for 24h and transcripts that were significantly regulated were identified. Wisp1 was identified as one of the genes most highly upregulated by TGFb1. To identify the transcriptional targets of Wisp1, 4T1 cells were then virally transduced to increase Wisp1 expression. The gene expression profiles of Wisp1-overexpressing 4T1 cells were determined and revealed that Wisp1 overexpression does not result in major gene expression changes in 4T1 cells.

2019-07-08 | GSE110912 | GEO

Breast tumor from Pik3caH1047R/+ mammary gland transduced with single or pooled lentivirus.

Project description:RNA-seq of breast tumor from Pik3caH1047R/+ mammary gland transduced with single or pooled lentivirus.

2018-11-18 | GSE122658 | GEO

miRNA profiling from T-ALL cells

Project description:The NOTCH1 signaling pathway is a critical determinant of cell fate decisions and drives oncogenesis through mechanisms that are incompletely understood. To elucidate tumorigenic pathways that cooperate with activated Notch1 in leukemogenesis,we performed miRNA expression profiling of normal CD4+CD8+ thymocytes, non-malignant ICN1 over-expressing CD4+CD8+ cells and ICN1-induced tumor CD4+CD8+ cells. Three groups of the murine T cells: Control CD4+CD8+ normal thymocytes vs.non-malignant ICN1-expressing CD4+CD8+ cells vs. ICN1-tumor CD4+CD8+ cells .

2011-02-19 | E-GEOD-27418 | biostudies-arrayexpress

Breast tumor from Pik3caH1047R/+ mammary gland transduced with single or pooled lentivirus.

Project description:Breast tumor from Pik3caH1047R/+ mammary gland transduced with single or pooled lentivirus.

| PRJNA505888 | ENA

miRNA profiling from T-ALL cells

2011-02-19 | GSE27418 | GEO

Identification of WISP1 as an important survival factor in human mesenchymal stem cells

Project description:WNT-induced secreted protein 1 (WISP1/CCN4), a member of the CCN protein family, acts as a downstream factor of the canonical WNT-signaling pathway. A dysregulated expression of WISP1 often reflects its oncogenic potential by inhibition of apoptosis, a necessary form of cell death that protect cell populations for transformation into malignant phenotypes. WISP1-signaling is also known to affect proliferation and differentiation of human mesenchymal stem cells (hMSCs), which are fundamental for the constitution and maintenance of the musculoskeletal system. Our study emphasizes the importance of WISP1-signaling for cell survival of primary human cells. Therefore, we established a successful down-regulation of endogenous WISP1 transcripts through gene silencing in hMSCs. We were able to demonstrate the consequence of cell death immediately after WISP1 down-regulation took place. Bioinformatical analyses of subsequent performed microarrays from WISP1 down-regulated vs. control samples confirmed this observation. We uncovered several clusters of differential expressed genes important for cellular apoptosis induction and immuno-regulatory processes, thereby indicating TRAIL-induced and p53-mediated apoptosis as well as IFNbeta-signaling. Since all of them act as potent inhibitors for malignant cell growth, in vitro knowledge about the connection with WISP1-signaling could help to find new therapeutic approaches concerning cancerogenesis and tumor growth in musculoskeletal tissues. We established a successful down-regulation of endogenous WISP1 transcripts through gene silencing in hMSCs. Knock-down versus controls.

2014-04-30 | E-GEOD-37603 | biostudies-arrayexpress

Hypoxia potentiates the inflammatory fibroblast phenotype promoted by pancreatic cancer cell-derived cytokines

Project description:Cancer-associated fibroblasts (CAFs) are a major cell type in the stroma of solid tumors and can exert both tumor-promoting and tumor-restraining functions. This functional heterogeneity is correlated with the existence of transcriptionally distinct subpopulations of CAFs. While CAF heterogeneity can be driven in part by tumor cell-produced cytokines, other determinants shaping CAF identity and function are largely unknown. Here, we investigated the role of hypoxia in regulating CAF heterogeneity in PDAC

2023-02-18 | GSE221761 | GEO

Gene expression profile of primary CLL cells transduced with a mutated form on NOTCH1 following IgM stimulation

Project description:In CLL, NOTCH1 is the most commonly mutated gene at diagnosis and it is associated with a poor outcome. The mechanisms underlying how NOTCH1 contributes to disease progression, resistance to treatment and Richter’s transformation remain largely unknown. Data suggests a link between BCR activation and NOTCH1 signalling so the main goal of this study is to compare the gene expression profile of primary CLL cells transduced with the intracellular part of NOTCH1 lacking of the PEST domain vs cells transduced with an empty vector following IgM stimulation.

2022-09-08 | GSE150595 | GEO

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