ArticleMolecular and cellular biochemistry2022
CAF-derived midkine promotes EMT and cisplatin resistance by upregulating lncRNA ST7-AS1 in gastric cancer.
Article in Molecular and cellular biochemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Molecular signals associated with intraperitoneal chemotherapy resistance in gastric cancer with peritoneal metastasis through PIPS GC trial integrated translational research.Scientific reports · 2025Trial
- Autophagy as a therapeutic target for cisplatin-resistant gastric cancer.Genes & diseases · 2026Review
- Rewiring immunity: Midkine's emerging role in cancer immune escape and drug resistance.iScience · 2026Review
- MDK Activates the PI3K/AKT Axis to Induce AP2A1 Expression and Epithelial-Mesenchymal Transition in Colorectal Cancer.Cancers · 2026Article
- Midkine (MDK) as a central regulator of the tumor microenvironment: From developmental cytokine to therapeutic target.Cancer letters · 2026Review
- Peritumoural adipose tissue drives immune evasion in colorectal cancer via adipose-mesenchymal transformation.Nature cell biology · 2026Article
- Mutation-Immune Crosstalk Contextualizes CAF-Associated ARPC1A Programs and Cisplatin Response in Gastric Cancer.Human mutation · 2026Article
- Remodeling the Stroma: The Role of ncRNAs in Cancer-Associated Fibroblasts and Therapeutic Implications for Digestive Tumors.Drug design, development and therapy · 2026Review
- Development and validation of a CAF-related signature for prognosis and therapy response in colorectal cancer: new insights on HSPB1.NPJ precision oncology · 2025Article
- LBX2-AS1 in acceleration of glycolysis and cancer angiogenesis via miR-491-5p/MDK signaling axis in colorectal cancer: an experimental study.Annals of medicine · 2025Article
- Multi-omics analysis unveils the role of cancer-associated fibroblasts in cutaneous squamous cell carcinoma.Cancer cell international · 2025Article
- Midkine Promotes Tumor Growth and Attenuates the Effect of Cisplatin in Small Cell Lung Cancer.Cancer medicine · 2025Article
- Midkine (MDK) in cancer and drug resistance: from inflammation to therapy.Discover oncology · 2025Review
- Multi-Transcriptomic Analysis Reveals GSC-Driven MES-Like Differentiation via EMT in GBM Cell-Cell Communication.Biomedicines · 2025Article
- Significance of Midkine Signaling in Women's Cancers: Novel Biomarker and Therapeutic Target.International journal of molecular sciences · 2025Review
- A narrative review of papillary thyroid carcinoma-related long non-coding RNAs and their relevance to malignant tumors.Translational cancer research · 2025Review
- Notable influences of estrogen and sex-specific microenvironment in colorectal cancer revealed by single-cell transcriptome analysis.International journal of medical sciences · 2025Article
- LncRNA in gastric cancer drug resistance: deciphering the therapeutic strategies.Frontiers in oncology · 2025Review
- Research on Correlations of lncRNA ST7-AS1 with Progression and Therapeutic Targets of Esophageal Cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
This study aimed to investigate the role of cancer-associated fibroblast (CAF)-derived midkine (MK) in cisplatin (DDP) resistance. The primary cultures of CAFs and non-cancer fibroblasts (NFs) were isolated and purified. The DDP-resistant gastric cancer (GC) cells were cultured with CAF-conditioned medium. QRT-PCR and Elisa assays were employed to determine MK expression. The expression of ST7-AS1 was measured by qRT-PCR. The impact of CAFs, MK, and ST7-AS1 silencing on DDP resistance was determined by MTT and Annexin V/PI staining assay. Expression of EMT markers and PI3K/AKT was determined by Western blot and qRT-PCR. The role of MK in DDP resistance was confirmed in a xenograft model. Incubation with CAF-conditioned medium increased the IC50 to DDP. Also, incubation with CAF-conditioned medium increased cell viability, reduced cell apoptosis, and promoted EMT in DDP-resistant GC cells, which were all blocked with MK neutralization antibody treatment. MK increased the DDP resistance and upregulated the expression of ST7-AS1 in DDP-resistant GC cells. Additionally, ST7-AS1 knockdown increased the sensitivity to DDP by inhibiting EMT. Moreover, ST7-AS1 knockdown significantly decreased the phosphorylation of PI3K and AKT, and suppressed EMT, which were restored by MK addition. Finally, MK promoted tumor growth and DDP resistance in a mice model bearing the SGC-7901/DDP xenografts. CAF-derived MK promotes EMT-mediated DDP resistance via upregulation of ST7-AS1 and activation of PI3K/AKT pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.