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Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer [array]

ABSTRACT: We examined the pathways that are regulated by TDO2 in APC-deficient cancer cells by analyzing gene expression profiles of APC-WT and APC-KO MC38 cells that are transduced with inducible shTDO2 constructs. This study establishs that the TDO2-Kyn-AhR axis serves a critical role in promoting APC-deficient tumor growth via cancer cell autonomous (metabolism and proliferation) and non-autonomous mechanisms (tumor immunity).

ORGANISM(S): Mus musculus

PROVIDER: GSE201415 | GEO | 2022/07/13

REPOSITORIES: GEO

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Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer I

Project description:We examined the pathways that are regulated by TDO2 in APC-deficient cancer cells by analyzing gene expression profiles of APC-WT and APC-KO MC38 cells that are transduced with inducible shTDO2 constructs. This study establishs that the TDO2-Kyn-AhR axis serves a critical role in promoting APC-deficient tumor growth via cancer cell autonomous (metabolism and proliferation) and non-autonomous mechanisms (tumor immunity).

2022-07-13 | GSE200908 | GEO

Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer [ChIP-Seq]

2022-07-13 | GSE201414 | GEO

Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer II

Project description:Comparative transcriptomic analysis of TAMs isolated from APC-WT and APC-KO MC38 orthotopic tumors express higher levels of multiple classical M2-like markers (CD163, CCL22, YM1) compared to APC-WT tumors after re-normalized the read counts of multiple M2 macrophage markers with housekeeping gene read counts (GAPDH and ACTB).

2022-07-13 | GSE200909 | GEO

Hypoxia and dimethyloxalylglycine (DMOG) downregulates tryptophan-2,3-dioxygenase (TDO2) expression in GBM cells

Project description:The tryptophan degrading enzyme TDO2 is downregulated upon HIF1alpha stabilization by exposure to both hypoxia as well as chemical hypoxia mimetics such as DMOG in glioblastoma cell line A172.

2019-12-29 | GSE138535 | GEO

Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells

Project description:Expression of tryptophan 2,3-dioxygenase (TDO) is a determinant of malignancy in gliomas through kynurenine (KYN) signaling. We report that inhibition of TDO activity attenuated recovery from replication stress and increased the genotoxic effects of bis-chloroethylnitrosourea (BCNU). Activation of the Chk1 arm of the replication stress response (RSR) was reduced when TDO activity was blocked prior to BCNU treatment, whereas phosphorylation of serine 33 (pS33) on replication protein A (RPA) was enhanced - indicative of increased fork collapse. Analysis of quantitative proteomic results revealed TDO-dependent changes in several pathways - including down-regulation of 53BP1 and sirtuin signaling. We went on to show that cells lacking TDO activity exhibited defective recruitment of 53BP1 to gamma-H2AX foci, which corresponded with delayed repair of DNA breaks. Addition of exogenous KYN increased the rate of break repair. TDO inhibition diminished SIRT7 deacetylase recruitment to chromatin, which increased histone H3K18 acetylation - a key mark involved in preventing 53BP1 recruitment to sites of DNA damage. These results highlight the potential for tumor-specific metabolic changes to influence genome stability and may have implications for glioma treatment strategies.

2021-09-09 | PXD022351 | Pride

Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer

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

2022-07-13 | GSE200910 | GEO

Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer

Project description:Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer

| PRJNA827168 | ENA

Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer II

Project description:Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer II

| PRJNA827171 | ENA

Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer I

Project description:Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer I

| PRJNA827172 | ENA

Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer [array]

Project description:Synthetic Essentiality of Tryptophan 2,3-dioxygenase 2 in APC-Mutated Colorectal Cancer [array]

| PRJNA831654 | ENA

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