BioID-based intact cell interactome of the Kv1.3 potassium channel identifies a Kv1.3-STAT3-p53 cellular signaling

Elena Prosdocimi1, Veronica Carpanese1, Luca Matteo Todesca1

  • 1Department of Biology, University of Padova, Padova, Italy.

Science Advances
|September 4, 2024
PubMed

Insights

The potassium channel Kv1.3 promotes tumor growth by interacting with STAT3 and p53 pathways. Inhibiting Kv1.3 in melanoma reduces tumor size and metastasis, revealing its role as a key signaling hub.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Kv1.3 is a potassium channel involved in various diseases, including cancer.
  • The precise role of Kv1.3 in cancer progression remains unclear.

Purpose of the Study:

  • To investigate the interactome of Kv1.3 in intact cells.
  • To elucidate the role of Kv1.3 and its interacting proteins in tumorigenesis.

Main Methods:

  • BioID proximity labeling to identify Kv1.3 interactors.
  • Generation of Kv1.3-ablated melanoma cell clones.
  • In vivo tumor growth and metastasis assays.
  • Analysis of mitochondrial function and signaling pathways.

Main Results:

  • Kv1.3 interacts with STAT3 and p53 signaling pathways.
  • Kv1.3 ablation in melanoma reduced tumor proliferation, colony formation, size, and metastasis.
  • Inhibition of Kv1.3 increased ROS, decreased STAT3 phosphorylation, stabilized p53, and altered cellular metabolism.

Conclusions:

  • Kv1.3 plays a tumor-promoting role through its interactome.
  • Targeting Kv1.3 offers a novel therapeutic strategy for cancer, addressing both its channel function and signaling hub roles.

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