ArticleOncoTargets and therapy2019
ARHGAP4 mediates the Warburg effect in pancreatic cancer through the mTOR and HIF-1α signaling pathways.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- ARHGAP36 serves as a diagnostic and therapeutic marker that mediates immune escape and promotes thyroid cancer metastasis.Biomedical reports · 2025Article
- Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.EBioMedicine · 2025Article
- Progression of mCell death discovery · 2024Review
- Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.bioRxiv : the preprint server for biology · 2024Article
- miR-939, as an important regulator in various cancers pathogenesis, has diagnostic, prognostic, and therapeutic values: a review.Journal of the Egyptian National Cancer Institute · 2024Review
- NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma.Scientific reports · 2024Article
- Rho GTPase-activating protein 4 is upregulated in Kidney Renal Clear Cell Carcinoma and associated with poor prognosis and immune infiltration.Cancer biomarkers : section A of Disease markers · 2024Article
- The role of hypoxic microenvironment in autoimmune diseases.Frontiers in immunology · 2024Review
- Article
- ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling.Oncogene · 2023Article
- Cancer-associated fibroblast-secreted miR-421 promotes pancreatic cancer by regulating the SIRT3/H3K9Ac/HIF-1α axis.The Kaohsiung journal of medical sciences · 2022Article
- Curcumin Sensitises Cancerous Kidney Cells to TRAIL Induced Apoptosis via Let-7C Mediated Deregulation of Cell Cycle Proteins and Cellular Metabolism.International journal of molecular sciences · 2022Article
- Action Sites and Clinical Application of HIF-1α Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- Glycolysis in the progression of pancreatic cancer.American journal of cancer research · 2022Review
- Analysis of ARHGAP4 Expression With Colorectal Cancer Clinical Characteristics and Prognosis.Frontiers in oncology · 2022Article
- Long non-coding RNAPeerJ · 2022Article
- The Intricate Crosstalk Between Insulin and Pancreatic Ductal Adenocarcinoma: A Review From Clinical to Molecular.Frontiers in cell and developmental biology · 2022Review
- ARHGAP4-SEPT2-SEPT9 complex enables both up- and down-modulation of integrin-mediated focal adhesions, cell migration, and invasion.Molecular biology of the cell · 2021Article
- Long non‑coding RNA PCED1B‑AS1 promotes pancreatic ductal adenocarcinoma progression by regulating the miR‑411‑3p/HIF‑1α axis.Oncology reports · 2021Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe phenomenon that cancer cells avidly exhibit glycolysis with lactate secretion and decrease in mitochondrial activity under aerobic conditions is known historically as the Warburg effect. Rho GTPase-activating protein 4 (ARHGAP4) is an important negative regulator of the Rho signaling pathway that was associated with the tumorigenesis. Our study aims to determine the function of ARHGAP4 in controlling the glycolytic process of pancreatic cancer in vitro and possible molecular mechanism involved.
methodsARHGAP4 and PKM2 expressions in pancreatic cancer tissues were measured by immunohistochemistry. Human pancreatic cancer cells transfected with ARHGAP4 expressing lentivirus or siRNA were treated with either mTOR inhibitor (Rapamycin) or HIF-1α inhibitor (YC-1), and the effects were analyzed on cell viability, glucose uptake, lactate release, and the levels of ARHGAP4, p-mTOR, mTOR, PKM2, and HIF-1α expression.
resultsOur findings showed that ARHGAP4 and PKM2 expressions were, respectively, down-regulated and up-regulated in pancreatic cancer tissues. Overexpression of ARHGAP4 significantly inhibited cell viability, glucose uptake, lactate release, PKM2 expression, and activation of mTOR and HIF-1α signaling pathways in pancreatic cancer cells while ARHGAP4 silencing and treatment of Rapamycin or YC-1 showed inverse effects. Additionally, ARHGAP4 downregulation induced cell morphology of pancreatic cancer was inhibited by Rapamycin or YC-1 treatment.
conclusionThese findings suggest that mTOR and HIF-1α signaling pathways can regulate the ARHGAP4-mediated glycolytic process of pancreatic cancer.
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