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Updated: Sep 24, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Midkine Promotes Metastasis and Therapeutic Resistance via mTOR/RPS6 in Uveal Melanoma

Margarete M Karg1,2, Lukas John1, Nasrin Refaian3

  • 1Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.

Molecular Cancer Research : MCR
|May 3, 2022
PubMed

Insights

Midkine, a cytokine found in uveal melanoma, promotes cancer cell survival and metastasis to the liver. Targeting midkine may offer new therapeutic strategies for this rare eye cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Ophthalmology

Background:

  • Uveal melanoma is a rare eye cancer with poor survival rates due to metastasis.
  • Current treatments face challenges due to widespread therapeutic resistance.
  • Identifying novel therapeutic targets is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of midkine in uveal melanoma.
  • To determine if midkine expression correlates with patient survival and metastasis.
  • To explore midkine as a potential therapeutic target and biomarker.

Main Methods:

  • Assessed midkine expression in primary uveal melanoma tissues.
  • Correlated midkine levels with patient survival, metastatic disease, and histopathologic parameters.
  • Utilized cell-based assays to study midkine's effects on cell survival, migration, and resistance to AKT/mTOR inhibition.
  • Investigated midkine's mechanism in mediating mTOR activation.

Main Results:

  • Midkine is expressed in uveal melanoma and its expression correlates with poor survival.
  • Elevated midkine levels are associated with metastatic disease and specific histopathologic features.
  • Midkine promotes uveal melanoma cell survival, migration, and resistance to AKT/mTOR inhibition.
  • Midkine mediates mTOR activation by maintaining RPS6 phosphorylation.

Conclusions:

  • Midkine acts as a survival factor in uveal melanoma, driving metastasis and therapeutic resistance.
  • Midkine represents a potential biomarker for predicting patient outcomes.
  • Targeting midkine could offer a novel therapeutic strategy for uveal melanoma.

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