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Verteporfin targets CCR5 to inhibit TNBC growth and metastasis via YAP1

ABSTRACT: Verteporfin targets CCR5 to inhibit TNBC growth and metastasis via YAP1

PROVIDER: PRJNA917518 | ENA |

REPOSITORIES: ENA

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Verteporfin targets CCR5 to inhibit TNBC growth and metastasis via YAP1

Project description:CCL5/CCR5 axis is an immunotherapeutic target for triple-negative breast cancer (TNBC). However, the signaling mechanism is poorly understood and its antagonists have not been reported. Here, we developed a high-throughput screening (HTS) assay for discovering its antagonists. Verteporfin was identified as a specific and more potent inhibitor than maraviroc. It significantly reduced TNBC tumor growth in an immunologically dependent manner, and lung metastasis in a cell-intrinsic way. Mechanistically, CCR5 was co-expressed with Yes-associated protein 1 (YAP1) in TNBC patients. RNA-sequencing and expression silencing further revealed that CCR5 promoted the expression of YAP1 through HIF-1α in TNBC cells, and through YAP1 to regulate β-catenin, ZEB1/ZEB2 for metastasis, as well as CXCL16 and CXCL8 for immune cell migration and tumor growth. In essence, verteporfin may have potential immunotherapeutic applications for diseases co-expressing CCR5 and YAP1 such as TNBC. The HTS assay can be adapted for unveiling antagonists of broader signaling pathways.

2024-01-25 | GSE222052 | GEO

Impact of Verteporfin on HCC cells

Project description:Together with TEAD4 the Hippo pathway effector YAP stimulates chromosomal instability. Verteporfin is known to disrupt the physical YAP/TEAD interaction and tehrefore might prevent from chromosomal instability in liver cancer. Immortalized HCC cell line hepG2 is treated with Verteporfin for 24 hours.

2016-02-11 | E-GEOD-73396 | biostudies-arrayexpress

Tumor selective proteotoxicity of verteporfin inhibits colon cancer progression independent of YAP1

Project description:Verteporfin (VP) inhibts colon cancer growth in vivo and in cell lines by inducing high molecular weight oligomerization of proteins. The antitumor effect of VP is independent of its YAP inhibitor activity. Tumor hypoxia contributes partly to antitumor effect of VP by impairing clearance of VP-induced high molecular weight aggregates.

2015-10-14 | PXD002793 | Pride

Differential Gene expression in CCR5+ versus CCR5- OT-I T cells

Project description:OT-I T cells were exposed to CpG ODN-activated CCR5ko Lymph nodes for 6 h, stained for surface CCR5 and FACS-sorted into CCR5+ and CCR5- fractions In the study presented here freshly isolated OT1 T cells were exposed for 6h at 37oC to teased-out CpG ODN-activated CCR5ko LNs in 96-well plates and stained for surface CCR5 before sorting into CCR5+ (Hua2) and CCR5- (Hua1) fractions. High quality total RNA isolated from each cell fraction using TRIZOL and Qiagen RNEasy kit per manufacture's recommendation was subjected to microarray analysis using the Affymetrix Mouse Gene ST 1.0 array chip to discover differentially expressed genes.

2016-01-14 | E-GEOD-76820 | biostudies-arrayexpress

Differential Gene expression in CCR5+ versus CCR5- OT-I T cells

Project description:OT-I T cells were exposed to CpG ODN-activated CCR5ko Lymph nodes for 6 h, stained for surface CCR5 and FACS-sorted into CCR5+ and CCR5- fractions

2016-01-14 | GSE76820 | GEO

Anti-cancer activity of verteporfin in cholangiocarcinoma

Project description:We investigated the antitumoral effect of verteporfin in YAP/AKT hydrodynamic tail vein injected murine models and we analyzed the correlative change of immune cell profile and stemness with the treatment of verteporfin by using flow cytometry and single-cell RNA sequencing

2023-04-21 | GSE229855 | GEO

CCR5 HIV controllers

Project description:CCR5 HIV controllers

| PRJEB48153 | ENA

Comprehensive analysis of molecular expression differences in NALM6 cells before and after use of verteporfin

Project description:Aims:This study used cell line models and patient datasets to investigate the role of YAP1 in B- ALL. Methods: We used RNA-Seq to compare the gene expression levels of the Hippo pathway-related molecules before and after verteporfin (VP) treatment to identify important Hippo pathway-related genes in the NALM6 cell line. Results:we identified a total of 2002 differentially expressed genes in VP and DMSO treatment groups (FC ≥ 1.5, p ≤ 0.05), including 1042 upregulated and 960 downregulated genes, of which 146 were associated with the Hippo signaling pathway. Further screening resulted in 29 identified genes comprising 12 upregulated and 17 downregulated genes, which were associated with VP-treated NALM6 cells. Conclusion:Pre- and post-VP treatment, the upstream gene LATS1 was upregulated, and its overexpression increased YAP1 Ser127 site phosphorylation further studies.

2024-11-01 | GSE231947 | GEO

People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells

Project description:CCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess detereminants of CCR5 expression. Percentages of CCR5 positive cells (%) and CCR5 mean fluorescence intensity (MFI) assessed by flow cytometry in monocytes and lymphocyte subsets were correlated to host factors, HIV-1 cell-associated (CA)-RNA and CA-DNA, plasma inflammation markers and metabolites.

2022-08-12 | PXD031628 | Pride

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Project description:Sequencing of 9kb of the CCR5 genomic locus in 15 patients who naturally control HIV infection

2021-12-07 | E-MTAB-11062 | biostudies-arrayexpress