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Na+/K+ ATPase activity promotes invasion of endocrine resistant breast cancer cells

Maitham A Khajah1, Princy M Mathew1, Yunus A Luqmani1

  • 1Faculty of Pharmacy, Kuwait University, Safat, Kuwait.

Plos One
|March 29, 2018
PubMed
Abstract

Insights

Inhibiting the Na+/K+-ATPase (NKP) in breast cancer cells reduced proliferation, motility, and invasion. Targeting NKP may offer a new therapeutic strategy for metastatic breast cancer.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • The Na+/K+-ATPase (NKP) is a crucial ion transporter implicated in signal transduction.
  • Altered NKP expression is observed in various cancers, including breast cancer.
  • This study investigates NKP inhibition in non-tumorigenic and breast cancer cell lines.

Purpose of the Study:

  • To evaluate the impact of inhibiting NKP activity on breast cancer cell behavior.
  • To explore NKP as a potential therapeutic target in breast cancer, particularly in metastatic cases.
  • To analyze the effects of NKP inhibition on cell proliferation, motility, invasion, and signaling pathways.

Main Methods:

  • Utilized RT-PCR, western blotting, and immunofluorescence for expression and localization analysis.
  • Assessed cell proliferation, apoptosis, and cell cycle via MTT, annexin V, and flow cytometry.
  • Quantified cell motility, invasion, and matrix metalloproteinase activity using wound healing, matrigel, and fluorescence assays.

Main Results:

  • NKP was primarily located on the cell membrane, with enhanced baseline expression and activity in breast cancer cells.
  • Ouabain and TTX treatment significantly inhibited NKP activity, reducing proliferation, motility, invasion, and membrane blebbing.
  • EGF stimulation caused NKP internalization, and ouabain inhibited downstream signaling pathways including Rac/cdc42, ERK1/2, and P70S6K.

Conclusions:

  • NKP activity is elevated in breast cancer and contributes to aggressive phenotypes.
  • Inhibiting NKP demonstrates significant anti-cancer effects on proliferation and metastasis.
  • Targeting NKP presents a promising therapeutic avenue for improving outcomes in metastatic breast cancer patients.

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