Effect of FSCN1 gene inactivation in the H295R cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE216008 | GEO | 2022/10/25
REPOSITORIES: GEO
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Project description:Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high risk of relapse and metastatisation. The actin-bundling protein fascin (FSCN1) is overexpressed in aggressive ACC and represents a reliable prognostic indicator. FSCN1 has been shown to synergize with the Rho/Rac GEF VAV2 in enhancing the invasion properties of ACC cancer cells. Based on those results, we investigated the effects of FSCN1 inactivation by CRISPR/Cas9 or pharmacological blockade on the invasive properties of ACC cells, both in vitro and in an in vivo metastatic ACC zebrafish model. Moreover, to assess the impact of FSCN1 inactivation on global gene and protein expression in H295R cells, we performed RNA-seq and proteomic profiling of control and FSCN1 knock-out (KO) clones.
2022-11-18 | MSV000090738 | MassIVE
Project description:<p>Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high risk of relapse and metastatisation. The actin-bundling protein fascin (FSCN1) is overexpressed in aggressive ACC and represents a reliable prognostic indicator. FSCN1 has been shown to synergize with the Rho/Rac GEF VAV2 in enhancing the invasion properties of ACC cancer cells. Based on those results, we investigated the effects of FSCN1 inactivation by CRISPR/Cas9 or pharmacological blockade on the invasive properties of ACC cells, both <em>in vitro</em> and in an <em>in vivo</em> metastatic ACC zebrafish model. Here we showed that FSCN1 is a transcriptional target for Beta-catenin in H295R ACC cells and that its inactivation resulted in defects in cell attachment and proliferation. Additionally, FSCN1 knock-out modulated the expression of genes involved in cytoskeleton dynamics and cell adhesion. When SF-1 dosage was upregulated in H95R cells, activating their invasive capacities, FSCN1 knock-out reduced the number of filopodia, lamellipodia/ruffles and focal adhesions, while decreasing cell invasion in Matrigel. Similar effects were produced by the FSCN1 inhibitor G2-044, which also diminished the invasion of ACC cell lines (CU-ACC2, JIL-2266, MUC-1) expressing lower levels of FSCN1 than H295R. In the zebrafish model, metastases formation was significantly reduced in FSCN1 knock-out cells and G2-044 significantly reduced the number of metastases formed by ACC cells. Our results indicate that FSCN1 represents a new druggable target for ACC and provide the rationale for future clinical trials with FSCN1 inhibitors in patients with ACC, possibly in combination with immunotherapy.</p>
2023-03-20 | MTBLS6402 | MetaboLights
Project description:Fascin actin-bundling protein 1 (FSCN1) is an evolutionarily conserved actin-bundling protein that plays a critical role in cell migration, motility, adhesion and cellular interactions. Although multiple clinical studies have implicated the expression of FSCN1 in laryngeal squamous cell carcinoma (LSCC) progression, the precise mechanism of FSCN1 in the process has not been clearly elucidated. To define FSCN1 function, we characterized FSCN1-interacting proteins in LSCC cells by immunoprecipitation followed by LC-MS/MS. After data filtering, 119 proteins with expression in both the Hep-2 and TU-177 cell samples were identified as FSCN1-interacting partners. With in-depth bioinformatics analysis, we linked FSCN1 to critical cellular processes including cell adhesion, glycolysis/gluconeogenesis, regulation of protein ubiquitination, ribosomal RNA processing and small molecule metabolism. We discuss the interactions between FSCN1 and some of the newly validated partners. The identification of these potential partners of FSCN1 expands our knowledge of the FSCN1 interactome and provides a valuable resource for understanding the functions of this protein in LSCC progression.
2019-09-09 | PXD013072 | Pride
Project description:Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor with a poor prognosis. Fascin actin-bundling protein 1 (FSCN1) has been reported to play a crucial role in LSCC development and progression, but the underlying molecular mechanisms remain unknown. Here, a whole transcriptome microarray analysis was performed to screen for differentially expressed genes in FSCN1 knockdown cells. We identified 1063 differentially expressed mRNA transcripts. Functional annotation revealed that these differentially expressed genes (DEGs) were involved in multiple biological functions such as transcriptional regulation, response to radiation, focal adhesion, ECM-receptor interaction, steroid biosynthesis, and others. Through co-expression and protein-protein interaction analysis, we linked FSCN1 to novel functions, including defense response to virus and steroid biosynthesis.
2024-02-17 | GSE255143 | GEO
Project description:Colorectal cancer (CRC) is a highly malignant tumor associated with a poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR expresses at a higher level in CRC than normal tissue and LYAR expression is closely associated with distant CRC metastasis. LYAR significantly promotes the migration and invasion of CRC cells in vitro, and reduction of LYAR expression in CRC cells inhibites xenograft tumor metastasis in vivo. Microarray analysis of LYAR knockdown (KD) cells combined with ChIP assay, gene reporter assay and rescue experiment indicate that FSCN1 (fascin actin-bundling protein 1, Fascin-1) serves as a new and key regulator of the LYAR-promoted migration and invasion of CRC cells. In addition, knockdown of FSCN1 significantly inhibites subcutaneous tumorigenesis of CRC cells. Moreover, we found that FSCN1 affects some key enzymes in lipid fatty acid metabolism such as FASN and SCD. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by up-regulating FSCN1 expression and further promoting fatty acid synthesis in CRC.
2021-07-26 | GSE180805 | GEO
Project description:Colorectal cancer (CRC) is a highly malignant tumor associated with poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR, a nucleolar protein, expresses at a higher level in CRC than adjacent normal tissue and LYAR expression is closely associated with distant CRC metastasis. LYAR not only significantly promotes the migration and invasion of CRC cells in vitro, also the knockdown (KD) of LYAR in CRC cells inhibits xenograft tumor metastasis in vivo. Microarray analysis of LYAR KD cells combined with ChIP assay, gene reporter assay and rescue experiment indicate that FSCN1 (encoding fascin actin-bundling protein 1, Fascin-1) serves as a new key regulator of the LYAR-promoted migration and invasion of CRC cells. Knockdown of FSCN1 significantly inhibits subcutaneous tumorigenesis of CRC cells, and leads to the down-regulation of FASN and SCD, genes encoding key enzymes in fatty acid synthesis. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by up-regulating FSCN1 expression and affecting fatty acid metabolism in CRC.
2021-07-17 | GSE180263 | GEO
Project description:Effect of FSCN1 gene inactivation in the H295R cell line
| PRJNA891702 | ENA
Project description:We used the H295R cell line, human adrenocortical cells, harboring a heterozygous CTNNB1 (beta-catenin) gene mutation affecting the GSK3 beta-phosphorylation site (S45P) and leading to constitutive transcriptional activity of beta-catenin-LEF/TCF. Whole-transcript gene expression was analyzed in three stable clones of H295R cells expressing a doxycycline-inducible shRNA targeting CTNNB1 mRNA and in a control clone, without or with doxycycline for 5 days.
2015-08-03 | E-MTAB-3330 | biostudies-arrayexpress
Project description:H295R human adrenocortical cells treated with or without angiotensin II (100 nM) for 3 hr. Keywords = adrenal angiotensin aldosterone Keywords: parallel sample
2004-11-19 | GSE1030 | GEO
Project description:Transcription factor 21 (TCF21) directly binds and regulates SF1 in tumor and normal adrenocortical cells, and both are involved in the development and steroidogenesis of the adrenal cortex. TCF21 is a tumor suppressor gene and its expression is reduced in malignant tumors. In adrenocortical tumors, it is less expressed in adrenocortical carcinomas (ACC) than in adrenocortical adenomas (ACA) and normal tissue. However, a comprehensive analysis to identify TCF21 targets have not yet been conducted in any type of cancer. In this study, we performed Chromatin Immunoprecipitation and Sequencing (ChIP-Seq) in adrenocortical carcinoma cell line (NCI-H295R) overexpressing TCF21, with the aim of identifying TCF21 new targets. The five most frequently identified sequences corresponded to the PRDM7, CNTNAP2, CACNA1B, PTPRN2 and KCNE1B genes. Validation experiments showed that, in NCI-H295R cells, TCF21 regulates gene expression positively in PRDM7 and negatively in CACNA1B. Recently, it was observed that the N-type calcium channel v2.2 (Cav2.2) encoded by CACNA1B gene is important in Angiotensin II signal transduction for corticosteroid biosynthesis in NCI-H295R adrenocortical carcinoma cells. Indeed, TCF21 inhibits CACNA1B and Cav2.2 expression in NCI-H295R. In addition, in a cohort of 55 adult patients with adrenocortical tumor, CACNA1B expression was higher in ACC than ACA, and was related to poor disease-free survival in ACC patients. These results suggest a mechanism of steroidogenesis control by TCF21 in adrenocortical tumor cells, in addition to the control observed through SF1 inhibition. Importantly, steroid production could impair tumor immunogenicity, contributing to the immune resistance described in adrenal cancer.
2022-06-30 | GSE179308 | GEO