ArticleGastroenterology2022
BZW1 Facilitates Glycolysis and Promotes Tumor Growth in Pancreatic Ductal Adenocarcinoma Through Potentiating eIF2α Phosphorylation.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.Cancer medicine · 2023Pooled it
- Post-Translational Modifications in Pancreatic Cancer: Mechanisms to Clinical Applications.Journal of gastroenterology and hepatology · 2026Review
- BZW1 Drives Immune Evasion in Lung Adenocarcinoma via Ferroptosis Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Review
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- Concurrent expression of glucose-6-phosphate dehydrogenase and secreted phosphoprotein 1 characterizes an aggressive and immunosuppressive tumor state in hepatocellular carcinoma.Frontiers in cell and developmental biology · 2026Article
- Targeting the unfolded protein response in cancer: mechanisms, small-molecule inhibitors, and translational challenges.Frontiers in immunology · 2026Review
- Endoplasmic reticulum stress-mediated programmed cell death in the tumor microenvironment.Cell death discovery · 2025Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Self-activated prodrug nanocomposites reprogramming lactic acid metabolism to initiate acidosis-endoplasmic reticulum stress cascade and potentiate immunogenic cell death for enhanced liver cancer therapy.Journal of nanobiotechnology · 2025Article
- Inhibition of integrin α3 suppresses gastric cancer progression via STAT3-mediated regulation of SLC1A5-dependent glutamine uptake.Journal of gastroenterology · 2025Article
- SP1-Mediated Glycolytic Reprogramming Promotes Tumorigenesis and Progression in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Research Advances of the Autophagy-Regulated Radiosensitivity.Cell proliferation · 2025Review
- STN1 facilitates metastasis by promoting transcription of EMT-activator ZEB1 in pancreatic cancer.Nature communications · 2025Article
- Modulation of Endoplasmic Reticulum Stress in Experimental Anti-Cancer Therapy.International journal of molecular sciences · 2025Review
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Overcoming Ferroptosis-Induced Exhaustion of NK Cells through Inhibition of the ATF3-Mediated Integrated Stress Response in Ovarian Cancer.International journal of biological sciences · 2025Article
- Heterogenous cancer-associated fibroblasts related tumor microenvironment marked by CD10/KLF4/TIAM1 were identified in pancreatic adenocarcinoma by integrated transcriptomics.Frontiers in immunology · 2025Article
- F-box proteins at the crossroads of ubiquitination and tumor immunity: regulatory networks and immunotherapy strategies.Frontiers in immunology · 2025Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsPancreatic ductal adenocarcinoma (PDAC) is characterized by severe metabolic stress due to fibrosis and poor vascularization. BZW1 is an eIF5-mimic protein involved in tumorigenesis and progression. The aim of this study was to investigate the role of BZW1 in metabolic stress resistance in PDAC.
methodsBZW1 expression was evaluated in human PDAC tissue microarray and PDAC cells. Glycolysis regulation of BZW1 and its correlation with glycolysis-related genes was analyzed. Tumor growth, cell proliferation, and apoptosis were evaluated in mice xenograft tumors and patient-derived organoids.
resultsThe results of bioinformatic screening identified that BZW1 was 1 of the top 3 genes favorable for tumor progression in PDAC. The analysis of our cohort confirmed that BZW1 was overexpressed in human PDAC tissues compared with nontumor tissues, and its abnormal expression was correlated with large tumor size and poor prognosis. BZW1 promoted cell proliferation and inhibited apoptosis in both mouse xenograft models and PDAC-derived organoids via facilitating glycolysis in the oxygen-glucose-deprivation condition. Mechanically, BZW1 served as an adaptor for PKR-like endoplasmic reticulum (ER) kinase (PERK), facilitated the phosphorylation of eIF2α, promoted internal ribosome entry site-dependent translation of HIF1α and c-Myc, and thereby boosted the Warburg effect. In organoid-based xenografts with high BZW1 levels, both the PERK/eIF2α phosphorylation inhibitor GSK2606414 and ISRIB significantly suppressed tumor growth and prolonged animal survival.
conclusionsBZW1 is a key molecule in the internal ribosome entry site-dependent translation of HIF1α/c-Myc and plays crucial roles in the glycolysis of PDAC. BZW1 might serve as a therapeutic target for patients with pancreatic cancer.
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