Midkine Functionality in Cancer Biology
Summary
Midkine is a developmentally regulated, heparin‐binding cytokine that is re‐expressed in a wide range of malignancies. In cancer biology, it functions as a pleiotropic growth factor promoting tumour cell proliferation, survival and migration. By binding to cell‐surface receptors such as receptor‐type protein tyrosine phosphatase ζ and nucleolin, midkine activates key signalling cascades including PI3K/Akt, MAPK and NF-κB pathways. It also fosters angiogenesis by stimulating endothelial cell migration and neo‐vascularisation, and drives epithelial–mesenchymal transition, thereby enhancing invasive and metastatic behaviour. Elevated midkine levels in serum or tumour microenvironments correlate with chemoresistance, disease progression and poor prognosis. Its immunomodulatory effects can suppress anti-tumour immunity and reshape the stromal compartment. These multifaceted actions make midkine both a promising biomarker for non-invasive cancer detection and a strategic target for novel therapies, underscoring its global significance in precision oncology.
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Midkine Functionality in Cancer Biology publication trend
The graph below shows the total number of articles in midkine functionality in cancer biology across all publications each year (not limited to Nature Index journals).
Technical terms
Midkine (MDK): A heparin‐binding cytokine with roles in cell growth, survival and migration, often reactivated in cancers.
Angiogenesis: The process by which new blood vessels form from existing ones, essential for tumour growth and nutrient supply.
Epithelial–mesenchymal transition (EMT): A biological programme enabling epithelial cells to acquire motile, invasive mesenchymal traits.
Biomarker: A measurable molecule indicating a biological state or condition, used here to detect cancer or predict drug response.
Pleiotropic: Exhibiting multiple different effects or functions within an organism.
References
- The role of midkine in health and disease. Frontiers in Immunology (2023).
- Role of Midkine in Cancer Drug Resistance: Regulators of Its Expression and Its Molecular Targeting. International Journal of Molecular Sciences (2023).
- A Receptor-like Protein-tyrosine Phosphatase PTPζ/RPTPβ Binds a Heparin-binding Growth Factor Midkine INVOLVEMENT OF ARGININE 78 OF MIDKINE IN THE HIGH AFFINITY BINDING TO PTPζ*. Journal of Biological Chemistry (1999).
- The Anti-HIV Cytokine Midkine Binds the Cell Surface-expressed Nucleolin as a Low Affinity Receptor*. Journal of Biological Chemistry (2002).
- Haptotactic Migration Induced by Midkine INVOLVEMENT OF PROTEIN-TYROSINE PHOSPHATASE ζ, MITOGEN-ACTIVATED PROTEIN KINASE, AND PHOSPHATIDYLINOSITOL 3-KINASE*. Journal of Biological Chemistry (2001).
- Midkine Is Regulated by Hypoxia and Causes Pulmonary Vascular Remodeling*. Journal of Biological Chemistry (2004).
- Serum midkine levels are increased in patients with various types of carcinomas. British Journal of Cancer (2000).
- Inhibition of the Growth Factor MDK/Midkine by a Novel Small Molecule Compound to Treat Non-Small Cell Lung Cancer. PLOS ONE (2013).
- Midkine Is a Potential Therapeutic Target of Tumorigenesis, Angiogenesis, and Metastasis in Non-Small Cell Lung Cancer. Cancers (2020).
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