FIBP maintains colorectal cancer cells stemness via demethylation of stemness genes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA412214 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To validate how FIBP influences stemness, we obtained the genome-wide methylation in HCT116-CSCs by an Illumina HumanMethylation450 BeadChip.
2017-09-27 | GSE104271 | GEO
Project description:The unfolded protein response (UPR) maintains endoplasmic reticulum (ER) homeostasis by sensing protein-folding stress and orchestrating cellular adaptation via the ER-transmembrane proteins IRE1, PERK and ATF6. Malignant cells can co-opt UPR signaling by IRE1 and PERK to sustain tumor growth; however, the importance of ATF6 in cancer remains poorly deciphered. We observed elevated ATF6 transcriptional activity in several cancers including colorectal carcinoma (CRC). Genetic silencing or small molecule inhibition of ATF6 blocked cell cycle progression and reduced viability of several human CRC cell lines in vitro and disrupted tumor progression in vivo. Unexpectedly, ATF6 interference also disabled Myc and Wnt signaling and reduced stemness. ATF6 inhibition attenuated growth of organoids derived from malignant but not normal human intestinal tissue, reducing Wnt-pathway activity and driving cellular differentiation. Wnt-surrogate agonism rescued the growth inhibitory phenotype of ATF6 interference. Our findings identify ATF6 as an unexpected facilitator of oncogenic Wnt signaling in CRC.
2024-08-12 | MSV000095581 | MassIVE
Project description:ZFP90 promotes colorectal carcinogenesis and stemness
| PRJNA497880 | ENA
Project description:Metastasis is the leading cause of cancer-related mortality. Cancer stem cells contribute to metastasis in the murine colon cancer models, but the underlying mechanisms are unclear. Here we report a Wnt ligand, Dickkopf2 (DKK2) is essential for colorectal cancer stemness. Genetic depletion of Dkk2 in intestinal epithelial or stem cells reduced tumorigenesis as well as expression of the stem cell marker gene Lgr5 in a model of colitis-associated cancer. Mechanistically, DKK2 activates c-Src followed by increased LGR5 expressing stem cells in colorectal cancer through degradation of HNF4α1. Splenic injection of DKK2-deficient cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases compared to the control cancer organoids in spite of the presence of oncogenic mutations in Apc, Kras and Tp53 genes. These findings suggest that DKK2 is required for stemness of colorectal cancer cells, which in turn contributes to metastasis.
2021-09-01 | GSE157645 | GEO
Project description:The unfolded protein response maintains endoplasmic reticulum (ER) homeostasis by sensing protein-folding stress and orchestrating cellular adaptation via the ER-transmembrane proteins IRE1, PERK and ATF6. Malignant cells can co-opt IRE1 and PERK to sustain growth; however, the importance of ATF6 in cancer remains poorly deciphered. We observed elevated ATF6 transcriptional activity in several cancers including colorectal carcinoma (CRC). Genetic silencing or small molecule inhibition of ATF6 blocked cell cycle progression and reduced viability of several human CRC cell lines in vitro and disrupted tumor progression in vivo. Unexpectedly, ATF6 interference disabled Wnt and Myc signaling and reduced stemness. ATF6 inhibition attenuated growth of organoids derived from malignant but not normal human intestinal tissue, decreasing Wnt-pathway activity and driving cellular differentiation. Wnt-surrogate agonism in a Wnt-dependent CRC organoid restored pathway activity and rescued growth under ATF6 blockade. Our findings identify ATF6 as an unexpected facilitator of oncogenic Wnt signaling in CRC.
2024-08-06 | GSE273988 | GEO
Project description:The unfolded protein response maintains endoplasmic reticulum (ER) homeostasis by sensing protein-folding stress and orchestrating cellular adaptation via the ER-transmembrane proteins IRE1, PERK and ATF6. Malignant cells can co-opt IRE1 and PERK to sustain growth; however, the importance of ATF6 in cancer remains poorly deciphered. We observed elevated ATF6 transcriptional activity in several cancers including colorectal carcinoma (CRC). Genetic silencing or small molecule inhibition of ATF6 blocked cell cycle progression and reduced viability of several human CRC cell lines in vitro and disrupted tumor progression in vivo. Unexpectedly, ATF6 interference disabled Wnt and Myc signaling and reduced stemness. ATF6 inhibition attenuated growth of organoids derived from malignant but not normal human intestinal tissue, decreasing Wnt-pathway activity and driving cellular differentiation. Wnt-surrogate agonism in a Wnt-dependent CRC organoid restored pathway activity and rescued growth under ATF6 blockade. Our findings identify ATF6 as an unexpected facilitator of oncogenic Wnt signaling in CRC.
2024-08-08 | GSE274172 | GEO
Project description:Dickkopf-2 regulates stemness and differentiation of colorectal cancer cells via c-Src and HNF4α1
| PRJNA662322 | ENA
Project description:Gastric cancer (GC) stem cells (GCSCs) are characterized as high level of ALDH activity, however, the mechanisms of maintenance of high ALDH activity and stemness in GCSCs are largely unknown. Here, we report that KDM4C, a H3K9me2/3-demethylase, epigenetically regulates ALDH1A3 by histone demethylation and forms a feed-forward loop with ALDH1A3 to supports GS stemness. Ectopic expression of both KDM4C and ALDH1A3 promotes the properties of GCSCs, including spherogenecity, self-renewal, CD44 expression and ALDH activity; knockdown of anyone abolished the effect of each other. KDM4C directly binds to the promoter of ALDH1A3, leads to histone demethylation, thereby promoting ALDH1A3 transcription. Upregulated ALDH1A3 in turn transcriptionally upregulates KDM4C. Simultaneous inhibition of KDM4C and ALDH1A3 synergistically sensitizes GC sphere-derived cells to traditional chemotherapeutic drugs. The finding that upregulated ALDH1A3 promotes its own transcription via KDM4C-mediated epigenetic modification represents an important feed-forward mechanism for GCSCs to maintain stemness and promote tumourigenesis and our work thus suggests a novel therapeutic strategy for eradicating human GCSCs. To investigate the mechanisms underlying KDM4C promoting CG stemness, we identified the differentially expressed proteins (DEPs) between KDM4C-overexpressing and control AGS cells by iTRAQ-based quantitative proteomic analysis.
2022-02-16 | PXD023455 | Pride
Project description:KMT9 controls growth and stemness of colorectal cancer
| PRJNA632605 | ENA
Project description:ZFP90 promotes colorectal carcinogenesis and stemness [RNA-seq]
| PRJNA497885 | ENA