ArticleScientific reports2017
Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of lncRNA ANRIL in tumour cells.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 106 citations in OpenAlex.
- Single-cell RNA sequencing reveals the tumor microenvironment and facilitates strategic choices to circumvent treatment failure in a chemorefractory bladder cancer patient.Genome medicine · 2020Trial
- Decoding the role of cancer-associated fibroblasts in cisplatin resistance of head and neck squamous cell carcinoma.iScience · 2026Review
- Rewiring immunity: Midkine's emerging role in cancer immune escape and drug resistance.iScience · 2026Review
- Midkine (MDK) as a central regulator of the tumor microenvironment: From developmental cytokine to therapeutic target.Cancer letters · 2026Review
- Remodeling the Stroma: The Role of ncRNAs in Cancer-Associated Fibroblasts and Therapeutic Implications for Digestive Tumors.Drug design, development and therapy · 2026Review
- Unraveling the impact of cancer-associated fibroblasts on lymphatic metastasis of head and neck squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.Journal of ovarian research · 2025Review
- Multi-omics analysis unveils the role of cancer-associated fibroblasts in cutaneous squamous cell carcinoma.Cancer cell international · 2025Article
- Exploring drug resistance via intercellular crosstalk using spatial transcriptomics in high-grade serous ovarian carcinoma.NPJ precision oncology · 2025Article
- Review
- Role of exosomal non‑coding RNAs in cancer‑associated fibroblast‑mediated therapy resistance (Review).International journal of oncology · 2025Review
- Midkine (MDK) in cancer and drug resistance: from inflammation to therapy.Discover oncology · 2025Review
- Significance of Midkine Signaling in Women's Cancers: Novel Biomarker and Therapeutic Target.International journal of molecular sciences · 2025Review
- Role of Hypoxia-Associated Long Noncoding RNAs in Cancer Chemo-Therapy Resistance.International journal of molecular sciences · 2025Review
- Fibroblast-immune crosstalk in oral squamous cell carcinoma: from tumor promotion to immune evasion.Frontiers in immunology · 2025Review
- Notable influences of estrogen and sex-specific microenvironment in colorectal cancer revealed by single-cell transcriptome analysis.International journal of medical sciences · 2025Article
- Review
- Monitoring melanoma patients on treatment reveals a distinct macrophage population driving targeted therapy resistance.Cell reports. Medicine · 2024Article
- Midkine: A Cancer Biomarker Candidate and Innovative Therapeutic Approaches.European journal of breast health · 2024Article
- Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.Vaccines · 2024Review
12 more citing papers are in PubMed but not listed here.
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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
Midkine (MK) is a heparin-binding growth factor that promotes carcinogenesis and chemoresistance. The tumour microenvironment (TME) can affect chemotherapy sensitivity. However, the role of stromal-derived MK, especially in cancer-associated fibroblasts (CAFs), is unclear. Here, we confirmed that MK decreased cisplatin-induced cell death in oral squamous cell carcinoma (OSCC) cells, ovarian cancer cells and lung cancer cells. We also isolated primary CAFs (n = 3) from OSCC patients and found that CAFs secreted increased levels of MK, which abrogated cisplatin-induced cell death. Moreover, MK increased the expression of lncRNA ANRIL in the tumour cells. Normal tissues, matched tumour-adjacent tissues and OSCC tissues were analysed (n = 60) and showed that lncRNA ANRIL was indeed overexpressed during carcinogenesis and correlated with both high TNM stage and lymph node metastasis (LNM). Furthermore, lncRNA ANRIL knockdown in tumour cells inhibited proliferation, induced apoptosis and increased cisplatin cytotoxicity of the tumour cells via impairment of the drug transporters MRP1 and ABCC2, which could be restored by treatment with human MK in a caspase-3/BCL-2-dependent manner. In conclusion, we firstly describe that CAFs in the TME contribute to the high level of MK in tumours and that CAF-derived MK can promote cisplatin resistance via the elevated expression of lncRNA ANRIL.
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