Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA361837 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cancer stem cells (CSCs), a small population of cancer cells, have been considered to be the origin of cancer initiation, recurrence, and metastasis. Tumor microenvironment provides crucial signals for CSCs to maintain stem cell properties and promote tumorigenesis. Therefore, establishment of an appropriate cell culture system to mimic the microenvironment for CSC studies is an important issue. In this study, we grew colon and hepatocellular carcinoma (HCC) cells on chitosan membranes and evaluated the tumor progression by transwell migration, drug resistance, microarray, and RT-PCR analysis. We also evaluated the CSC properties by flow cytometry, sphere forming assay, luciferase reporter assay, western blot, and gene knockdown. Experimental results showed that culturing cancer cells on chitosan increased cell motility, drug resistance, quiescent population, self-renewal capacity, and the expression levels of stemness and CSC marker genes, such as OCT4, NANOG, CD133, CD44, and EpCAM. Furthermore, we demonstrated that chitosan might activate canonical Wnt/β-catenin-CD44 axis signaling in CD44positive colon cancer cells and noncanonical Wnt-STAT3 signaling in CD44negative HCC cells. In conclusion, chitosan as culture substrates activated the essential signaling of CSCs and promoted CSC properties. The chitosan culture system provides a convenient platform for the research of CSC biology and screening of anticancer drugs.
2017-01-18 | GSE93704 | GEO
Project description:Massive studies have been applied in exploring the factors driving pathogenesis, progression and metastasis of hepatocellular carcinoma. However these studies were inefficient in disclosing the fundamental mechanism which promotes hepatocellular carcinoma. Zinc and zinc-finger proteins have been important in extensive biological processes for human. Supervised machine learning using bootstrapping algorithm on GEO and TCGA transcriptome data for hepatocellular carcinoma identified zinc-finger like protein ZFPL1 as potential hepatocellular carcinoma driver. Further studies validated ZFPL1 significantly promoted progression and metastasis of hepatocellular carcinoma. We performed RNA-seq on si-ZFPL1 xenograft tissue and identified CLDN3 as potential target gene for ZFPL1. Further experiments confirmed interaction between ZFPL1 and WNT signaling pathway markers. Conclusively, these studies indicated the effect and mechanism of ZFPL1 on promoting progression and metastasis of hepatocellular carcinoma and might gap the bridge between zinc-finger like proteins and hepatocellular carcinoma.
2024-10-19 | GSE277010 | GEO
Project description:The orphan nuclear receptor NR2E3 (Nuclear receptor subfamily 2 group E, Member 3) is an epigenetic player essential for p53 activation during liver injuries through its modulation of chromatin accessibility. Nonetheless, a precise tumor suppressive and epigenetic role of NR2E3 in hepatocellular carcinoma (HCC) remains unclear. HCC patients expressing low NR2E3 exhibit unfavorable clinical outcomes, aligning with heightened activation of the WNT/β-catenin signaling pathway. The murine HCC models utilizing NR2E3 knockout mice consistently exhibits accelerated liver tumor formation and progression accompanied by enhanced activation of WNT/β-catenin signaling pathway and inactivation of p53 signaling pathway. At cellular level, the loss of NR2E3 increases the acquisition of aggressive cancer cell phenotype and tumorigenicity and upregulates key genes in the WNT/β-catenin pathway with enhanced chromatin accessibility. This event is mediated through increased formation of active transcription complex involving Sp1, β-catenin, and p300, a histone acetyltransferase, on the promoters of target genes. These findings demonstrate that the loss of NR2E3 promotes WNT/β-catenin signaling activation at cellular, organismal, and clinical levels. In summary, NR2E3 is a novel tumor suppressor that maintains epigenetic homeostasis, thereby preventing activation of WNT/β-catenin signaling that promotes HCC formation and progression.
2024-08-26 | GSE243020 | GEO
Project description:ZFPL1 drives hepatocellular carcinoma through CLDN3 in WNT signaling pathway
| PRJNA1160216 | ENA
Project description:<p>The whole exome sequencing showed that HERC5 deletion and under-expression associates with shorter: time to tumor recurrence, progression-free, and overall survival in hepatocellular carcinoma (HCC) in two independent studies (p1=0.004, HR1=1.80; p2=0.018, HR2=3.31) totaling 286 HCC patients. Matched primary and recurrent tumors indicated a clonal selection advantage in somatic single nucleotide and copy number variants (CNVs) in recurrent compared to primary tumors of Chinese HCC patients with Wnt signaling most activated.</p>
| phs000782 | dbGaP
Project description:RABIF promotes hepatocellular carcinoma progression through regulation of mitophagy and glycolysis
| PRJNA1165735 | ENA
Project description:Sharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-κB signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here, we report novel mechanisms of HCC progression through Sharpin overexpression. Sharpin was upregulated in human HCC tissues. Increased Sharpin expression enhanced hepatoma cell invasion, whereas decrease in Sharpin expression by RNA interference inhibited invasion. Microarray analysis identified that versican, a chondroitin sulfate proteoglycan that plays crucial roles in tumor progression and invasion, was also upregulated in stably Sharpin-expressing cells. Versican expression increased in the majority of HCC tissues and knocking down of versican greatly attenuated hepatoma cell invasion. Sharpin expression resulted in a significant induction of versican transcription synergistically with Wnt/-catenin pathway activation. Furthermore, Sharpin overexpressing cells had high tumorigenic properties in vivo. These results demonstrate that Sharpin promotes versican expression synergistically with the Wnt/-catenin pathway, potentially contributing to HCC development. A Sharpin/versican axis could be an attractive therapeutic target for this currently untreatable cancer.
2017-01-23 | GSE87149 | GEO
Project description:The recent classification of colon cancer into molecular subtypes revealed that patients with the poorest prognosis harbor tumors with the lowest levels of Wnt signaling. This is contrary to the long-standing understanding that overactive Wnt signaling promotes tumor progression from early initiation stages through to the later stages including invasion and metastasis. Here, we lower the levels of Wnt signaling in SW480 and SW620 colon cancer cell lines via interference with two different steps in Wnt signaling that lie upstream or downstream of the effector protein ß-catenin. We find that these Wnt-reduced lines exhibit a more aggressive disease phenotype, including increased mobility in vitro and localized invasion in an orthotopic mouse model. RNA sequencing reveals that interference with Wnt signaling leads to an upregulation of gene programs that favor cell migration and invasion. We identify a set of upregulated genes common among the Wnt perturbations, and find that elevated expression of these genes is strongly predictive of poor patient outcomes in early-invasive colon cancer. These genes may have clinical applications as either patient biomarkers or new drug targets to be used in concert with existing therapies.
2019-12-31 | GSE130236 | GEO
Project description:Serine-threonine kinase receptor-associated protein (STRAP) is upregulated in breast, colorectal and lung cancers, promoting their growth. We identify the upregulation of STRAP in hepatocellular carcinomas. Elevated STRAP endows tumor cells with growth advantage by reprograming a variety of metabolic processes and signaling pathways critical for hepatocellular carcinoma progression. Especially, enhanced Wnt/β-catenin signaling is likely to be a major effector of its tumor-promoting role.
2018-09-03 | GSE101061 | GEO
Project description:Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway. Here we report that the modeled dynamics of the response to AXT050 revealed that receptor trafficking is sufficient to explain the effect of Met-integrin interactions on HGF signaling. Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients.
Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
2020-03-20 | MODEL2003200001 | BioModels