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Updated: Jun 29, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

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Inactivation of kindlin-3 increases human melanoma aggressiveness through the collagen-activated tyrosine kinase

Coralie Reger De Moura1,2, Baptiste Louveau1,2, Fanélie Jouenne1,2

  • 1Department of Pharmacology and Tumor Genomics, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, F-75010, Paris, France.

Oncogene
|April 3, 2024
PubMed

Insights

Kindlin-3 loss enhances melanoma growth by disrupting collagen signaling through DDR1, impacting cell adhesion, proliferation, and migration. This reveals a new therapeutic target for melanoma treatment.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Kindlin-3 is a focal adhesion protein crucial for integrin activation.
  • Its tumor suppressor role and interaction mechanisms in melanoma progression require further elucidation.
  • Understanding kindlin-3 inactivation's impact on melanoma and its microenvironment is critical.

Purpose of the Study:

  • To investigate the role of kindlin-3 inactivation in BRAF-mutant melanoma.
  • To elucidate the interaction mechanisms between kindlin-3, collagen signaling, and DDR1.
  • To explore kindlin-3's impact on melanoma cell oncogenic properties and tumor growth.

Main Methods:

  • Kindlin-3 knockdown and somatic mutations were induced in BRAF V600mut melanoma cells.
  • Cell adhesion, proliferation, and migration were assessed in vitro.
  • Tumor growth was evaluated in vivo in mice.
  • Interactions between kindlin-3, DDR1, and β1-integrin were analyzed.

Main Results:

  • Kindlin-3 inactivation increased melanoma cell proliferation, migration, and tumor growth.
  • Kindlin-3 loss decreased cell adhesion via collagen-related signaling.
  • Kindlin-3 interacts with DDR1, modulating its expression and β1-integrin interaction.
  • Kindlin-3 loss disrupted the DDR1/β1-integrin complex and enhanced DDR1 inhibition efficacy.
  • Kindlin-3 downregulation correlated with DDR1 overexpression and poorer melanoma prognosis.

Conclusions:

  • Kindlin-3 acts as a tumor suppressor in melanoma by regulating collagen-activated DDR1 signaling.
  • Kindlin-3 inactivation promotes oncogenic properties through DDR1/β1-integrin complex disruption.
  • Targeting the kindlin-3/DDR1 axis offers a potential therapeutic strategy for melanoma.

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