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Molecular Activation of the Kv11.1 Channel Reprograms EMT in Colon Cancer by Inhibiting TGFβ Signaling via Activation

Najmeh Eskandari1,2, Vitalyi Senyuk1, Jennifer Moore1

  • 1Division of Hematology Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

Cancers
|December 10, 2021
PubMed

Insights

Activating the Kv11.1 potassium channel with NS1643 inhibits colon cancer cell migration by reversing epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET). This reprogramming blocks TGFβ signaling, reducing cancer stemness and cell motility.

Area of Science:

  • Cellular Biology
  • Oncology
  • Ion Channel Physiology

Background:

  • Cellular homeostasis relies on ionic gradients, yet ion channel roles in cancer remain underexplored.
  • The epithelial-to-mesenchymal transition (EMT) is crucial for cancer cell migration and metastasis.

Purpose of the Study:

  • To investigate the role of the Kv11.1 potassium channel in colon cancer cell migration.
  • To determine if Kv11.1 activity can reverse EMT and inhibit cancer cell motility.

Main Methods:

  • Pharmacological stimulation of Kv11.1 using NS1643.
  • Analysis of EMT/MET markers (SNAIL1, SLUG, TWIST, ZEB, N-cadherin, E-cadherin).
  • Investigation of TGFβ signaling pathway, R-SMADs, PP2B (calcineurin), and cancer stem cell markers (NANOG, SOX2, OCT4).

Main Results:

  • NS1643 significantly inhibited colon cancer cell motility.
  • Kv11.1 activation reversed EMT to MET, decreasing mesenchymal markers and increasing E-cadherin.
  • NS1643 suppressed TGFβ signaling by activating PP2B, leading to R-SMAD de-phosphorylation.
  • Inhibition of cancer stemness markers and G0/G1 cell cycle arrest were observed.

Conclusions:

  • Kv11.1 channel activation reprograms EMT to MET via TGFβ signaling inhibition.
  • This mechanism effectively reduces colon cancer cell motility and stemness.
Keywords:
TGFβ-signalingcalcineurincolon cancermigrationpotassium channels

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