Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ACKR3 Degradation by the Novel Scutellarein Derivative TBS6b Potently Suppresses Hepatocellular Carcinoma

ABSTRACT: Hepatocellular carcinoma (HCC) remains a formidable challenge in oncology due to its aggressive nature and limited treatment options. Scutellarein, derived from the traditional Chinese herb Scutellaria baicalensis, has shown potential against HCC, albeit with limited efficacy. To enhance its therapeutic potential, we synthesized a novel scutellarein derivative, TBS6b, incorporating the antitumor active moieties trimethoxyphenyl and benzimidazole. TBS6b exhibited significantly enhanced anti-HCC activity, surpassing its precursor in both in vitro and in vivo models. Comprehensive assays, including colony formation, EdU incorporation, wound healing, and Transwell migration, demonstrated TBS6b's potent inhibition of HCC proliferation, migration, and invasion. Notably, TBS6b's mechanism of action was elucidated as promoting the ubiquitination and subsequent degradation of the atypical chemokine receptor 3 (ACKR3), a key regulator of HCC's aggressive behavior. Rescue experiments further confirmed that ACKR3 downregulation is central to TBS6b’s anti-cancer efficacy. This study not only identifies ACKR3 as a novel therapeutic target in HCC but also introduces TBS6b as a promising candidate for HCC treatment, offering a new avenue for therapeutic intervention in this lethal disease.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Cell Culture

DISEASE(S): Carcinoma

SUBMITTER: Xiaonan Yang

LAB HEAD: Xiaonan Yang

PROVIDER: PXD053819 | Pride | 2024-08-16

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Result.zip	Other
	TEclipse_FAIMS_TMT_F1.raw	Raw
	TEclipse_FAIMS_TMT_F10.raw	Raw
	TEclipse_FAIMS_TMT_F2.raw	Raw
	TEclipse_FAIMS_TMT_F3.raw	Raw

Items per page:

1 - 5 of 11

Similar Datasets

Comparison of two hepatocellular cancer cell lines with distinct properties regarding epithelial-mesenchymal transition

Project description:The epithelial to mesenchymal transition (EMT) of malignant hepatocytes is a crucial event in hepatocellular carcinoma (HCC) progression and recurrence. We aimed to establish a human model of EMT to examine drug efficacy and specificity in HCC progression. Human HCC cell populations were characterized by immunofluorescence analysis, migration and invasion assays, array comparative genomic hybridization, whole-genome expression profiling and promoter methylation. Therapeutic agents clinically used against HCC were examined for efficacy by determination of IC50 values. Liver cancer cell lines showed either an epithelial or mesenchymal phenotype of which latter showed strong migratory and invasive abilities in vitro. The common cellular origin of both cell types indicated that mesenchymal HCC cells have been derived from epithelial hepatocytes through EMT in the HCC patient. Drug exposure of mesenchymal HCC cells showed higher resistance to the targeted therapeutic agents sorafenib and erlotinib as compared to epithelial HCC cells, which were slightly more resistant to cytostatic drugs. Most remarkably, combined treatment with doxorubicin and sorafenib caused increased susceptibility of both HCC cell types resulting in enhanced drug efficacy. Taken together, this novel model of human HCC allows to monitor the differential effect of liver cancer progression on drug efficacy in pre-clinical studies. hepatocellular carcinoma cell lines HCC-1.2 and HCC-1.1 cells, referred to as 3p and 3sp cells, respectively, were isolated from one HCC patient as described ( Sagmeister S, Eisenbauer M, Pirker C, et al. New cellular tools reveal complex epithelial-mesenchymal interactions in hepatocarcinogenesis. Br J Cancer 2008;99(1):151-9.). 3p cells of passages 10 to 12 and 3sp cells of passages 7 to 13 are termed 3p early and 3sp early, respectively. 3p cells between passage 71 and 76 and 3sp from passage 72 to 87 were termed 3p late and 3sp late, respectively

2011-11-21 | E-GEOD-26391 | biostudies-arrayexpress

ALK inhibitors suppress HCC and synergize with anti-PD-1 therapy and ABT-263 in preclinical models

Project description:Hepatocellular carcinoma (HCC) currently lacks effective therapies, leaving a critical need for new treatment options. A previous study identified the Anaplastic Lymphoma Kinase (ALK) amplification in HCC patients, raising the question of whether ALK inhibitors could be a viable treatment. Here, we showed that both ALK inhibitors and ALK knockout effectively halted HCC growth in cell cultures. Lorlatinib, a potent ALK inhibitor, suppressed HCC tumor growth and metastasis across various mouse models. Additionally, in an advanced immunocompetent humanized mouse model, when combined with an anti-PD-1 antibody, lorlatinib more potently suppressed HCC tumor growth, surpassing individual drug efficacy. Lorlatinib induced apoptosis and senescence in HCC cells, and the senolytic agent ABT-263 enhanced the efficacy of lorlatinib. Additional studies identified that the apoptosis-inducing effect of lorlatinib was mediated via GGN and NRG4. These findings establish ALK inhibitors as promising HCC treatments, either alone or in combination with immunotherapies or senolytic agents.

2024-04-29 | GSE178211 | GEO

Comparison of two hepatocellular cancer cell lines with distinct properties regarding epithelial-mesenchymal transition

2011-11-21 | GSE26391 | GEO

MicroRNA-Based Classification of Hepatocellular Carcinoma and Oncogenic Role of miR-517a

Project description:Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations. Herein, we report the first molecular classification of 89 HCC based on the expression of 358 microRNAs and integrative genomic analysis. Three main subclasses of HCC were identified : two of them were associated with beta-catenin mutations or aggressive phenotype. A subset of the subclass of aggressive tumors (8/89, 9%) showed overexpression of a cluster of microRNAs located on chr19q13.41 (C19MC locus. We showed that miR 517a, representing C19MC, promoted cell proliferation, migration and invasion in vitro and induced the development of aggressive tumors in vivo suggesting its role as a novel oncogenic driver in HCC. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2011-02-17 | E-GEOD-20596 | biostudies-arrayexpress

Therapeutic efficacy of FASN inhibition in preclinical models of HCC

Project description:Therapeutic efficacy of FASN inhibition in preclinical models of HCC

| PRJNA783327 | ENA

MicroRNA-Based Classification of Hepatocellular Carcinoma and Oncogenic Role of miR-517a

2011-02-17 | GSE20596 | GEO

Therapeutic efficacy of FASN inhibition in preclinical models of HCC

Project description:Background & Aims: Aberrant activation of fatty acid synthase (FASN) is a major metabolic event during the development of HCC. We evaluated the therapeutic efficacy of TVB3664, a novel FASN inhibitor, either alone or in combination, for HCC treatment. Approach & Results: The therapeutic efficacy and the molecular pathways targeted by TVB3664, either alone or with tyrosine kinase inhibitors or the checkpoint inhibitor anti-PD-L1 antibody, were assessed in human HCC cell lines and multiple oncogene-driven HCC mouse models. RNAseq was performed to characterize the global gene expression and metabolic profiles. TVB3664 effectively ameliorated the fatty liver phenotype in the aged mice and AKT activation-induced hepatic steatosis. TVB3664 monotherapy showed moderate efficacy in NASH-related murine HCCs, induced by loss of PTEN and c-MET overexpression. TVB3664, in combination with cabozantinib, triggered tumor regression in this mouse HCC model but did not improve the responsiveness to immunotherapy. Global gene expression revealed that TVB3664 predominantly modulated metabolic processes, while TVB3664 synergized with cabozantinib to downregulate multiple cancer-related pathways, especially the AKT/mTOR pathway and cell proliferation genes. TVB3664 also improved the therapeutic efficacy of sorafenib and cabozantinib in the FASN-dependent c-MYC HCC model. However, TVB3664 had no efficacy nor synergistic effects in FASN-independent mouse HCC models. Conclusions: This preclinical study suggests the limited efficacy of targeting FASN as monotherapy for HCC treatment. However, FASN inhibitors could be combined with other drugs for improved effectiveness. These combination therapies could be developed based on the driver oncogenes, supporting precision medicine approaches for HCC treatment.

2022-01-28 | GSE189529 | GEO

Oncogenic Functions of the Transcription Factor LSF

Project description:Overexpression of LSF in less aggressive hepatocellular carcinoma (HCC) cells resulted in highly aggressive, angiogenic and multi-organ metastatic tumors while inhibition of LSF significantly abrogated growth and metastasis of highly aggressive HCC cells in nude mice. We used microarrays to identify the downstream genes mediating the effects of LSF in HCC cells. Gene expression profiles were compared between Control-8 and LSF-17 clones of HepG3 cells.

2010-04-06 | E-GEOD-19815 | biostudies-arrayexpress

Cell motility and migration as determinants of stem cell efficacy

Project description:Limited stem cell migration capacities and undirected homing hamper their therapeutic efficacy. We report here the novel technology to isolate stem cell subpopulations with high migration potential. Hereby, we identified podoplanin-dependent stem cell mobility as important mechanism for their in vivo homing capacities and therapeutic efficacy as validated in preclinical models of AlzheimerÃ‚Â´s disease and mouse glioma. In vivo applications of highly migrating stem cells resulted in remarkable improvement of targeted homing and engraftment rates. Moreover, animals receiving highly migrating stem cells showed higher recovery rates compared to unselected stem cells. This novel technology provides useful tool to improve therapeutic efficacy of stem cells and give insights into stem cell subpopulations heterogeneity with the potential of general applicability for cellular therapies.

| EGAS00001002478 | EGA

Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells [gene expression]

Project description:There is an urgent need for developing more effective therapies for aggressive hepatocellular carcinoma (HCC). Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi) currently in clinical trials for HCC and shows greater stability and performance over first generation DNMTis. The aim of this study is to identify potential therapeutic targets of SGI-110 for clinical trials.

2018-06-26 | GSE105065 | GEO