Downregulation of <scp>ADAMTS3</scp> Suppresses Stemness and Tumorigenicity in Glioma Stem Cell

Kim, Hyun‐Jin; Jeong, Hang Yeon; Batara, Don Carlo; Moon, Changjong; Lee, Seongsoo; Lee, Suk Jun; Park, Sang‐Ik; Choi, Moon‐Chang; Kim, Sung‐Hak

doi:10.1111/cns.14052

Cited by 3 publications

(1 citation statement)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ADAMTS3 participates in normal physiological processes, like the embryonic development, tissue remodeling and wound healing [ 48 ]. A study by Kim et al reported that ADAMTS3 was highly expressed in glioma stem cells and significantly correlated with its tumorigenic and proliferative activities [ 49 ]. However, at present, no study has reported the correlation between ADAMTS3 and HCC.…”

Section: Discussionmentioning

confidence: 99%

Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis

Jiang,

Zhu,

Tan

et al. 2024

Aging

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis

Jiang,

Zhu,

Tan

et al. 2024

Aging

View full text Add to dashboard Cite

Downregulation of ADAMTS3 Suppresses Stemness and Tumorigenicity in Glioma Stem Cell

et al. 2022

View full text Add to dashboard Cite

Aims Glioblastoma multiforme (GBM) is the most aggressive type of human brain tumor, with a poor prognosis and a median overall survival of fewer than 15 months. Glioma stem cells (GSCs) have recently been identified as a key player in tumor initiation and therapeutic resistance in GBM. ADAMTS family of metalloproteinases is known to cleave a wide range of extracellular matrix substrates and has been linked to tissue remodeling events in tumor development. Here, we investigate that ADAMTS3 regulates GSC proliferation and self‐renewal activities, and tumorigenesis in orthotopic xenograft models. Methods ADAMTS3 mRNA expression levels in normal human astrocyte (NHA), glioma, and GSCs cell lines were compared. After knockdown of ADAMTS3, alamarBlue assay, in vitro limiting dilution, and orthotopic xenograft assays were performed. To investigate the tumor‐associated roles of ADAMTS3, several statistical assays were conducted using publicly available datasets. Results ADAMTS3 level was remarkably higher in GSCs than in NHA, glioma cell lines, and their matched differentiated tumor cells. Interestingly, knockdown of ADAMTS3 disrupted GSC's proliferation, self‐renewal activity, and tumor formation in vivo. Furthermore, ADAMTS3 could be used as an independent predictor of malignancy progression in GBM. Conclusion We identified ADAMTS3 as a potential therapeutic target for GBM.

show abstract

Multi-Omics Pan-Cancer Analysis of Procollagen N-Propeptidase Gene Family of ADAMTS as Novel Biomarkers to Associate with Prognosis, Tumor Immune Microenvironment, Signaling Pathways, and Drug Sensitivities

Chen,

Xiao,

Fan

et al. 2024

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

Background: The extracellular matrix (ECM) modeling induced by the metalloproteinases is a vital characteristic for tumor progression. Previous studies mainly focus on the functions of two subgroups of metalloproteinases: matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs) in tumors. The roles of another important group: the ADAMs with thrombospondin motifs (ADAMTS) remain unclear. This study aimed to perform a pan-cancer analysis of procollagen N-propeptidase subgroup of ADAMTS (PNPSA). Methods: We systematically analyzed expression landscape, genomic variations, prognostic value, and cell expression clusters of PNPSA in pan-cancer based on the multiple integrated open databases. Besides, we also analyzed the impacts of expressions and genomic variations of PNPSA members on tumor immune microenvironment (TIME) and immune-related molecules in pan-cancer based on the immune-related open databases. The Gene Set Variation Analysis (GSVA) was performed to evaluate the associations of the whole PNPSA with prognosis, tumor indicators, TIME, and drug sensitivities. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to reveal related signaling pathways. Finally, immunohistochemical staining was used to validate the differential analysis results. Results: We found a dual prognostic role of PNPSA members in pan-cancer and they were significantly correlated with TIME and immune-related molecules. Interestingly, the copy number variations (CNVs) of all PNPSA members were revealed to be negatively correlated with NK cell infiltration in most cancers. Single-cell sequencing analysis reveals expressions of PNPSA gene family members on some specific tumor and immune cells in addition to the fibroblasts. The GSVA score was found to have some predictive value for survival status in Brain Lower Grade Glioma (LGG), Mesothelioma (MESO), and Uveal Melanoma (UVM) and to be significantly correlated with tumorigenesis-related pathways such as PI3K-Akt, AGE-RAGE, etc. The GSVA score also shows some predictive value for chemotherapy and immunotherapy efficacy in some tumors. Conclusions: PNPSA was correlated with tumor development and might be potential tumor biomarker and therapeutic target.

show abstract

Downregulation of ADAMTS3 Suppresses Stemness and Tumorigenicity in Glioma Stem Cell

Cited by 3 publications

References 32 publications

Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis

Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis

Downregulation of ADAMTS3 Suppresses Stemness and Tumorigenicity in Glioma Stem Cell

Multi-Omics Pan-Cancer Analysis of Procollagen N-Propeptidase Gene Family of ADAMTS as Novel Biomarkers to Associate with Prognosis, Tumor Immune Microenvironment, Signaling Pathways, and Drug Sensitivities

Contact Info

Product

Resources

About