ArticleJournal of experimental & clinical cancer research : CR2019
Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
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- Silencing the Signal: The Metastasis Suppressor NDRG1 Disrupts Small Extracellular Vesicle-Mediated Crosstalk in Pancreatic Cancer.Journal of extracellular vesicles · 2026Article
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- Combining network pharmacology and experimental validation to study the action and mechanism of brusatol against lung adenocarcinoma.Scientific reports · 2026Article
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- Hedyotis diffusa Willd suppresses hepatocellular carcinoma tumor-stromal interactions by inactivating cancer-associated hepatic stellate cells.Journal of gastrointestinal oncology · 2026Article
- Genetic Regulation of ERK1/2-c-Fos Signalling Pathway in Newcastle Disease Virus-Induced Apoptosis of Human Pancreatic Cancer Stem Cells.The Malaysian journal of medical sciences : MJMS · 2026Article
- Particulate matter 2.5 promotes bladder cancer cell migration and invasion through the crosstalk between integrin-mediated MAPK/ERK and Wnt/β-catenin pathways.Particle and fibre toxicology · 2026Article
- Exploring the interplay between protein conformational changes and phosphorylation in a pancreatic cancer cell and stellate cell coculture system.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Identification and experimental validation of biomarkers associated with paraptosis in meningioma.Medicine · 2025Article
- Tumor Microenvironment: Recent Advances in Immunotherapies of Pancreatic Cancer.Medicina (Kaunas, Lithuania) · 2025Review
- High-mobility network hydrogel microsphere system to combat chondrocyte senescence for enhanced cartilage repair and regeneration.Materials today. Bio · 2025Article
- Genome-Wide Network Analysis of DRG-Sciatic Nerve Network-Inferred Cellular Senescence and Senescence Phenotype in Peripheral Sensory Neurons.Molecular neurobiology · 2025Article
- Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The mechanistic study of codonopsis pilosula on laryngeal squamous cell carcinoma based on network pharmacology and experimental validation.Frontiers in pharmacology · 2025Article
- Recent Advances in Signaling Pathways and Kinase Inhibitors for Leukemia Chemotherapy.Current medicinal chemistry · 2025Review
- TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Nanomedicine regulating PSC-mediated intercellular crosstalk: Mechanisms and therapeutic strategies.Acta pharmaceutica Sinica. B · 2024Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExtracellular signal-regulated kinases (ERKs) have been related to multiple cancers, including breast cancer, hepatocellular cancer, lung cancer and colorectal cancer. ERK1/2 inhibitor can suppress growth of KRAS-mutant pancreatic tumors by targeting cancer cell. However, no studies have shown the expression of ERK1/2 on pancreatic stromal and its effect on pancreatic cancer-stromal interaction.
methodsImmunohistochemistry and western blotting were performed to detect the expression of p-ERK1/2 in pancreatic tissues and cells. Cell viability assay was used to study IC50 of ERK inhibitor on pancreatic cancer cells (PCCs) and primary cancer-associated pancreatic stellate cells (PSCs). Transwell migration, invasion, cell viability assay, senescence β-galactosidase staining were performed to determine the effect of ERK inhibitor on PCCs and PSCs in vitro and in vivo. The expression of key factors involved in autophagy and epithelial-to-mesenchymal transition (EMT) process were evaluated by western blotting. The expression of key factors related to cell invasiveness and malignancy were confirmed by qRT-PCR. Co-transplantation of PCC Organoid and PSC using a splenic xenograft mouse model was used to evaluated combined treatment of ERK inhibitor and autophagy inhibitor.
resultsImmunohistochemical staining in pancreatic tumor samples and transgenetic mice detected p-ERK1/2 expression in both cancer cells and stromal cells. In pancreatic tissues, p-ERK1/2 was strongly expressed in cancer-associated PSCs compared with cancer cells and normal PSCs. PSCs were also significantly more sensitive to ERK1/2 inhibitor treatment. Inhibition of ERK1/2 suppressed EMT transition in HMPCCs, upregulated cellular senescence markers, activated autophagy in cancer-associated PSCs; and suppressed cancer-stromal interaction, which enhanced invasiveness and viability of cancer cells. We also found that chloroquine, an autophagy inhibitor, suppressed ERK inhibition-induced autophagy and promoted PSC cellular senescence, leading to significantly decreased cell proliferation. The combination of an ERK inhibitor and autophagy inhibitor suppressed liver metastasis in a splenic pancreatic cancer organoid xenograft mouse model.
conclusionsThese data indicate that inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis.
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