STRAP is involved in mutated Apc-induced stemness and tumorigenesis in colon cancer
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ABSTRACT:
PROVIDER: PRJNA673189 | ENA |
REPOSITORIES: ENA
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Project description:To identify pathways mediating the effects of Strap in colon cancer development, we established the mRNA expression profiles of intestinal adenomas that formed in ApcMin/+ mice with and without Strap deletion.
2021-09-20 | GSE160428 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24575: Beta-arrestin-2 deficiency effect on intestinal tumorigenesis in Apc-mutated mice GSE24576: Gene expression analysis of tumors from ApcD14/+ mice Refer to individual Series
2012-01-20 | E-GEOD-24577 | biostudies-arrayexpress
Project description:Purpose: Serine-threonine kinase receptor-associated protein (STRAP) plays an important role in neural development but also in tumor growth. Neuroblastoma, a tumor of neural crest origin, is the most common extracranial malignancy of childhood, and it continues to carry a poor prognosis. The recent discovery of the role of STRAP in another pediatric solid tumor, osteosarcoma, and its known function in neural development, led us to investigate the role of STRAP in neuroblastoma tumorigenesis. Methods: STRAP protein expression was abrogated in two human neuroblastoma cell lines, SK-N-AS (AS) and SK-N-BE(2). Methods included transient knockdown with siRNA, stable knockdown with shRNA lentiviral transfection, and CRISPR-Cas9 genetic knockout of STRAP. STRAP knockdown and knockout cells were examined for phenotypic alterations in vitro and tumor growth in vivo. Results: Cell proliferation, viability, motility, and growth were significantly decreased in STRAP knockout compared to wild-type cells. Indicators of stemness, including mRNA abundance of common stem cell markers Oct4, Nanog, and Nestin, the percentage of cells expressing CD133 on their surface, and the ability to form tumorspheres, were significantly decreased in the STRAP KO cells. In vivo, AS STRAP knockout cells formed tumors less readily than wild-type tumor cells. Conclusion: These novel findings demonstrated that STRAP plays a role in tumorigenesis and maintenance of neuroblastoma stemness.
2021-07-14 | GSE169322 | GEO
Project description:Amoung their pleiotropic functions, a role was recently assigned for b-arrestin scaffold proteins in tumor growth, angiogenesis and invasion. In order to elucidate the roles of b-arrestins in tumour developement in intestinal epithelium initiated by Apc mutation, we determined the effects of b-arrestin gene deletion on intestinal polypolis using ApcD14/+ mice, a relevant mouse model of human intestinal tumorigenesis.Here we show that unlike b-arrestin1, absence of b-arrestin2 dramatically decreased the number of spontaneously developping intestinal tumors in ApcD14/+ mice.The size of residual tumors was similarto that of controls, suggesting that their growth is b-arrestin2-independent. This result demonstrated a role for b-arrestin2 in the early development of a tumor subset. Gene expression profils analysis of ApcD14/+:Arrb2+/+ and ApcD14/+:Arrb2-/- tumors showed two distinct clusters among ApcD14/+:Arrb2+/+ tumors and one of them was statistically more correlated to ApcD14/+:Arrb2-/- tumors than to the other ApcD14/+:Arrb2+/+ cluster, eventhough a number of genes saw their expression affected in ApcD14/+:Arrb2-/- tumors only. Altogether, our data unravel an unexpected early diversity among intestinal tumors and a crucial role for b-arrestin2 in early tumor development in Apc-mutated mice. 16 tumors from ApcD14/+:Arrb2+/+ mice and 13 tumors from ApcD14/+:Arrb2-/- mice
2012-01-20 | E-GEOD-24575 | biostudies-arrayexpress
Project description:Amoung their pleiotropic functions, a role was recently assigned for b-arrestin scaffold proteins in tumor growth, angiogenesis and invasion. In order to elucidate the roles of b-arrestins in tumour developement in intestinal epithelium initiated by Apc mutation, we determined the effects of b-arrestin gene deletion on intestinal polypolis using ApcD14/+ mice, a relevant mouse model of human intestinal tumorigenesis.Here we show that unlike b-arrestin1, absence of b-arrestin2 dramatically decreased the number of spontaneously developping intestinal tumors in ApcD14/+ mice.The size of residual tumors was similarto that of controls, suggesting that their growth is b-arrestin2-independent. This result demonstrated a role for b-arrestin2 in the early development of a tumor subset. Gene expression profils analysis of ApcD14/+:Arrb2+/+ and ApcD14/+:Arrb2-/- tumors showed two distinct clusters among ApcD14/+:Arrb2+/+ tumors and one of them was statistically more correlated to ApcD14/+:Arrb2-/- tumors than to the other ApcD14/+:Arrb2+/+ cluster, eventhough a number of genes saw their expression affected in ApcD14/+:Arrb2-/- tumors only. Altogether, our data unravel an unexpected early diversity among intestinal tumors and a crucial role for b-arrestin2 in early tumor development in Apc-mutated mice.
2012-01-20 | GSE24575 | GEO
Project description:The tumor suppressor gene adenomatous polyposis coli (APC) is mutated in most colorectal cancers (CRC) resulting in constitutive Wnt activation. To understand the Wnt-activating mechanism of APC mutation, we applied CRISPR/Cas9 technology to engineer various APC-truncated isogenic lines. We find that the β-catenin inhibitory domain (CID) in APC represents the threshold for pathological levels of Wnt activation and tumor transformation. Mechanistically, CID-deleted APC truncation promotes β-catenin deubiquitination through reverse binding of β-TrCP and USP7 to the destruction complex. USP7 depletion in APC-mutated CRC inhibits Wnt activation by restoring β-catenin ubiquitination, drives differentiation and suppresses xenograft tumor growth. Finally, the Wnt-activating role of USP7 is specific to APC mutations, thus can be used as tumor-specific therapeutic target for most CRCs.
2017-11-09 | PXD007947 | Pride
Project description:Tankyrase, a poly(ADP-ribose) polymerase family member, regulates multiple cellular processes. Tankyrase inhibitors efficiently suppress APC-mutated colorectal cancer (CRC) cell proliferation. To examine the mechanism of anti-proliferative effect of tankyrase inhibitors (G007LK and RK582), we analyzed gene expression profiles of patient-derived APC-mutated CRC cells (JC21 and JC475) left untreated or treated with 0.3 µM G007LK or RK582 for 24 h by cDNA microarray analysis.
2024-01-17 | GSE232209 | GEO
Project description:The contribution of deubiquitylating enzymes to b-Catenin stabilisation in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, we report the deubiquitylase USP10 as APC-truncation- specific regulator enhancer of b-Catenin stability, potentiating WNT signalling pathway in CRC and cancer stem cells. Mechanistically, interaction studies in various CRC cell lines and in vitro binding studies, together with computational modelling, revealed that USP10 binding to b-Catenin is mediated via its USP10 unstructured N-terminus and requires truncated in the absence of full-length APC. Notably, loss of USP10 in CRISPR engineered intestinal organoids reduces tumorigenic properties of CRC cells and organoids, and blocks the super competitor-properties of APC-mutated intestinal cells, elicits induces the expression of differentiation genes, and opposes the APC-truncated phenotype in an intestinal hyperplasia model of D.melanogaster. Taken together, our findings reveal USP10s role in intestinal tumourigenesis by stabilising b-Catenin, leading to aberrant WNT signalling, enhancing cancer cell stemness and implicate the DUB USP10 as a cancer specific therapeutic vulnerability in Apc truncated CRC.
2024-01-01 | GSE226364 | GEO
Project description:We evaluated the gene expression profiles of Pirc rats (mutated for the APC gene) at one month of age, prior to the development of visible preneoplastic tumors or lesions. The analysis was performed on both female and male animals, comparing Pirc rats with wild type F344 rats of the same age.
2021-07-30 | E-MTAB-10016 | biostudies-arrayexpress
Project description: Not available
| S-EPMC3775784 | biostudies-literature