To Detach, Migrate, Adhere, and Metastasize: CD97/ADGRE5 in Cancer

Aust, Gabriela; Zheng, Leyu; Quaas, Marianne

doi:10.3390/cells11091538

Cited by 21 publications

(18 citation statements)

References 93 publications

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“…ALCAM is involved in the adhesion and migration of cancer cells and the interaction between cancer cells and immune cells [47,48]. In contrast, Adgre5 modulates the interaction between cancer cells and immune cells by suppressing the immune response [49]. Therefore, targeting these proteins could disrupt the interaction between cancer cells and the microenvironment, leading to decreased tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Analysis of heterogeneity in subpopulations of breast cancer using single-cell RNA sequencing

2023

Preprint

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Breast cancer is a complex disease with high levels of intra-tumor heterogeneity. Single-cell RNA sequencing (scRNA-seq) can identify the gene expression profile of different cell subpopulations, revealing key subpopulations that drive tumor progression and therapeutic resistance. We analyzed single-cell RNA-seq data from 26 primary tumors from three major clinical breast cancer subtypes. We inferred copy number variation (CNV) and identified 8 clusters of malignant epithelial cells, with Cluster 1 being the most widely present in breast cancer. We identified 28 subpopulations based on gene-expression profiles, with five subpopulations shared by multiple patients. We identified specific ligand-receptor interactions between different subpopulations and identified key pathway-associated prognostic markers, including EPHA3, JAML, LCK, and SEMA3B, which could serve as potential biomarkers. The tumor microenvironment plays a significant role in tumor growth and metastasis. Targeting proteins involved in the interaction between cancer cells and the microenvironment, including ALCAM, CD6, and Adgre5, has shown promise in preclinical cancer models. This study could provide valuable information to identify biomarkers for individualized cancer therapy, which is challenging due to high levels of intra-tumor heterogeneity.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Analysis of heterogeneity in subpopulations of breast cancer using single-cell RNA sequencing

2023

Preprint

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“…Alternative splicing of ADGRE5 mRNA generates three distinct isoforms that differ in the number of epidermal growth factor (EGF)-like repeats in the N-terminal extracellular domain (ECD) of the receptor ( Figure 1M ). 25 Analysis of TCGA RNA-seq data indicated that isoform 3, with four EGF repeats in the N-terminus, is the predominant variant in GBM ( Figure 1N ). CD97 transcript was found in all transcriptional subtypes of GBM in TCGA ( Supp.…”

Section: Resultsmentioning

confidence: 98%

“…CD97 is expressed in several lineages of the immune system, where it is critical for the inflammatory response, [20][21][22][23][24] as well as in multiple liquid and solid malignancies. 13,[25][26][27][28] Among these malignancies is GBM, in which CD97 was previously implicated in cellular proliferation, brain invasion, and tumor metabolism. [29][30][31][32][33] However, its mechanism of action in GBM remains incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability

Ravn-Boess,

Roy,

Hattori

et al. 2023

Preprint

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SUMMARYGlioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their functional role in gliomagenesis and their potential as treatment targets. To identify therapeutically targetable opportunities among aGPCR family members in unbiased fashion, we analyzed expression levels of all aGPCRs in GBM and non-neoplastic brain tissue. Using bulk and single cell transcriptomic and proteomic data, we show that CD97 (ADGRE5), an aGPCR previously implicated in GBM pathogenesis, is the most promising aGPCR target in GBM, by virtue of its abundance in all GBM tumors and itsde novoexpression profile in GBM compared to normal brain tissue and neural progenitors. CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures (PDGC)in vitroandin vivo. Transcriptomic and metabolomic data from PDGCs suggest that CD97 promotes glycolytic metabolism. The oncogenic and metabolic effects of CD97 are mediated by the MAPK pathway. Activation of MAPK signaling depends on phosphorylation of the cytosolic C-terminus of CD97 and recruitment of β-arrestin. Using single-cell RNA-sequencing and biochemical assays, we demonstrate that THY1/CD90 is the most likely CD97 ligand in GBM. Lastly, we show that targeting of PDGCs with an anti-CD97 antibody-drug conjugatein vitroselectively kills tumor cells but not human astrocytes or neural stem cells. Our studies identify CD97 as an important regulator of tumor metabolism in GBM, elucidate mechanisms of receptor activation and signaling, and provide strong scientific rationale for developing biologics to target it for therapeutic purposes.

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“…One of the key issues in treating cancer is to prevent tumor cells from invading and metastasizing ( 38 ). The scratch assay and Transwell assay were applied to detect the effect of BJP-2 on the migration of HepG-2 cells.…”

Section: Resultsmentioning

confidence: 99%

A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro

2022

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Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. And then BJP-2 was identified by SEC-MALLS-RI, GC-MS, methylation and NMR for the following characteristics: molecular weight of 6.42 × 104 Da, monosaccharide composition of glucuronic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), xylose (Xyl), glucuronic acid (GlcA), glucose (Glc), fucose (Fuc) and mannose (Man) with the percentage of 39.78, 31.93, 16.86, 6.43, 1.86, 1.28, 1.02, 0.61, and 0.23%, as well as the main chain of → 5)-α-L-Araf (1 → 4)-β-D-Gal(1 → , T-α-L-Araf (1 → 4)-β-D-Gal(1 → , and → 4)-α-L-6MeGalAp(1 → . The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. The analysis by MTT and flow cytometry showed that BJP-2 suppressed cell proliferation by inducing apoptosis in a concentration-dependent manner. Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent.

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To Detach, Migrate, Adhere, and Metastasize: CD97/ADGRE5 in Cancer

Cited by 21 publications

References 93 publications

WITHDRAWN: Analysis of heterogeneity in subpopulations of breast cancer using single-cell RNA sequencing

WITHDRAWN: Analysis of heterogeneity in subpopulations of breast cancer using single-cell RNA sequencing

The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability

A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro

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