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Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [TCF ChIP]

ABSTRACT: Akt2;Dlx5 double transgenic mice develops T-ALL, and these cells have up regulated Cholesterol synthesis via Wnt pathway for survival

ORGANISM(S): Mus musculus

PROVIDER: GSE149347 | GEO | 2020/10/07

REPOSITORIES: GEO

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Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [WTvsDP mouse RNA-seq]

Project description:Akt2;Dlx5 double transgenic mice develops T-ALL, and these cells have up regulated Cholesterol synthesis via Wnt pathway for survival

2020-10-07 | GSE149349 | GEO

Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [mouse PKF RNA-seq]

Project description:Akt2;Dlx5 double transgenic mice develops T-ALL, and these cells have up regulated Cholesterol synthesis via Wnt pathway for survival

2020-10-07 | GSE149348 | GEO

Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [primary tumor RNA-seq]

Project description:Akt2;Dlx5 double transgenic mice develops T-ALL, and these cells have up regulated Cholesterol synthesis via Wnt pathway for survival

2020-10-07 | GSE149346 | GEO

Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [human PKF RNA-seq]

Project description:Akt2;Dlx5 double transgenic mice develops T-ALL, and these cells have up regulated Cholesterol synthesis via Wnt pathway for survival

2020-10-07 | GSE149345 | GEO

Wnt signaling mediates oncogenic synergy between Akt and Dlx5 in T-cell lymphomagenesis by enhancing cholesterol synthesis.

Project description:The Dlx5 homeobox gene was first implicated as an oncogene in a T-ALL mouse model expressing myristoylated (Myr) Akt2. Furthermore, overexpression of Dlx5 was sufficient to drive T-ALL in mice by directly activating Akt and Notch signaling. These findings implied that Akt2 cooperates with Dlx5 in T-cell lymphomagenesis. To test this hypothesis, Lck-Dlx5;Lck-MyrAkt2 transgenic mice were generated. MyrAkt2 synergized with Dlx5 to greatly accelerate and enhance the dissemination of T-lymphomagenesis. RNA-seq analysis performed on lymphomas from Lck-Dlx5;Lck-MyrAkt mice revealed upregulation of genes involved in the Wnt and cholesterol biosynthesis pathways. Combined RNA-seq and ChIP-seq analysis of lymphomas from Lck-Dlx5;Lck-MyrAkt mice demonstrated that β-catenin directly regulates genes involved in sterol regulatory element binding transcription factor 2 (Srebf2)-cholesterol synthesis. These lymphoma cells had high Lef1 levels and were highly sensitive to β-catenin and Srebf2-cholesterol synthesis inhibitors. Similarly, human T-ALL cell lines with activated NOTCH and AKT and elevated LEF1 levels were sensitive to inhibition of β-catenin and cholesterol pathways. Furthermore, LEF1 expression positively correlated with expression of genes involved in the cholesterol synthesis pathway in primary human T-ALL specimens. Together, these data suggest that targeting β-catenin and/or cholesterol biosynthesis, together with AKT, could have therapeutic efficacy in a subset of T-ALL patients.

| S-EPMC7522078 | biostudies-literature

Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-10-07 | GSE149350 | GEO

Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [TCF ChIP]

Project description:Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [TCF ChIP]

| PRJNA628087 | ENA

Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis

Project description:Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis

| PRJNA628090 | ENA

Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [mouse PKF RNA-seq]

Project description:Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [mouse PKF RNA-seq]

| PRJNA628086 | ENA

Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [human PKF RNA-seq]

Project description:Wnt Signaling Mediates Oncogenic Synergy Between Akt and Dlx5 in T-Cell Lymphomagenesis by Enhancing Cholesterol Synthesis [human PKF RNA-seq]

| PRJNA628089 | ENA

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