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Updated: Jun 14, 2025

Probing High-density Functional Protein Microarrays to Detect Protein-protein Interactions
Published on: August 2, 2015
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.
Abstract:
Kv1.3 is a multifunctional potassium channel implicated in multiple pathologies, including cancer. However, how it is involved in disease progression is not fully clear. We interrogated the interactome of Kv1.3 in intact cells using BioID proximity labeling, revealing that Kv1.3 interacts with STAT3- and p53-linked pathways. To prove the relevance of Kv1.3 and of its interactome in the context of tumorigenesis, we generated stable melanoma clones, in which ablation of Kv1.3 remodeled gene expression, reduced proliferation and colony formation, yielded fourfold smaller tumors, and decreased metastasis in vivo in comparison to WT cells. Kv1.3 deletion or pharmacological inhibition of mitochondrial Kv1.3 increased mitochondrial Reactive Oxygen Species release, decreased STAT3 phosphorylation, stabilized the p53 tumor suppressor, promoted metabolic switch, and altered the expression of several BioID-identified Kv1.3-networking proteins in tumor tissues. Collectively, our work revealed the tumor-promoting Kv1.3-interactome landscape, thus opening the way to target Kv1.3 not only as an ion-conducting entity but also as a signaling hub.
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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