ArticleCell death & disease2022
ARHGEF2/EDN1 pathway participates in ER stress-related drug resistance of hepatocellular carcinoma by promoting angiogenesis and malignant proliferation.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
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- Remodelling the tumour microenvironment and beyond: ERO1A as a multifaceted regulator and emerging therapeutic target in cancer.Clinical and translational medicine · 2026Review
- SNHG7 interacts with PCBP2 to promote CDKN2A expression and modulate cuproptosis in colorectal cancer.Translational oncology · 2026Article
- Single-cell multi-omic analysis of mitochondrial mutational mosaicism and dynamics.Nature communications · 2026Article
- miR-22-Galectin-1 as an integral signaling axis in regulating metabolism and immunity in HCC.Biomarker research · 2026Article
- Unravelling the Phosphorylation Landscape of Anthrax Toxin Receptor 1: Mechanisms and Functional Insights Through Phosphoproteomic Data Integration.The protein journal · 2025Article
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- Inhibition of the long non-coding RNA MALAT1 downregulates MAP2K1, suppressing the progression of hypopharyngeal squamous cell carcinoma.Biomolecules & biomedicine · 2025Article
- EDN1 facilitates cisplatin resistance of non-small cell lung cancer cells by regulating the TNF signaling pathway.World journal of surgical oncology · 2025Article
- Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis.BMC cancer · 2025Article
- Endoplasmic reticulum stress-related super enhancer promotes epithelial-mesenchymal transformation in hepatocellular carcinoma through CREB5 mediated activation of TNC.Cell death & disease · 2025Article
- Physiological premature aging of ovarian blood vessels leads to decline in fertility in middle-aged mice.Nature communications · 2025Article
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming.Frontiers in oncology · 2025Review
- Targeting endoplasmic reticulum stress-induced CLGN resensitizes hepatocellular carcinoma to apoptosis: paeonol synergistically enhances efficacy by dual inhibition of CLGN and NF-κB.Frontiers in oncology · 2025Article
- Si-Wu-Tang improves liver fibrosis by restoring liver sinusoidal endothelial cell functionality and reducing communication with hepatic stellate cells.Chinese medicine · 2024Article
- Will AMPK be a potential therapeutic target for hepatocellular carcinoma?American journal of cancer research · 2024Review
- Development of a Combined Oxidative Stress and Endoplasmic Reticulum Stress-Related Prognostic Signature for Hepatocellular Carcinoma.Combinatorial chemistry & high throughput screening · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress is widely involved in the drug resistance of hepatocellular carcinoma (HCC), but the mechanism of ER stress-induced drug resistance involves multiple signaling pathways that cannot be fully explained. Exploring genes associated with ER stress could yield a novel therapeutic target for ER stress-induced drug resistance. By analyzing RNA-sequencing, ATAC-sequencing, and Chip-sequencing data of Tunicamycin (TM)-treated or untreated HCC cells, we found that Rho guanine nucleotide exchange factor 2 (ARHGEF2) is upregulated in HCC cells with ER stress. ARHGEF2 plays an active role in tumor malignant progression. Notwithstanding, no research has been done on the link between ER stress and ARHGEF2. The function of ARHGEF2 as a novel downstream effector of ER stress in the angiogenesis and treatment resistance of HCC was revealed in this work. ARHGEF2 overexpression was linked to malignant development and a poor prognosis in HCC. ER stress stimulates the expression of ARHGEF2 through upregulation of ZNF263. Elevated ARHGEF2 accelerates HCC angiogenesis via the EDN1 pathway, enhances HCC cell proliferation and tumor growth both in vitro and in vivo, and contributes to ER stress-related treatment resistance. HCC cell growth was more inhibited when ARHGEF2 knockdown was paired with targeted medicines. Collectively, we uncovered a previously hidden mechanism where ARHGEF2/EDN1 pathway promotes angiogenesis and participates in ER stress-related drug resistance in HCC.
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