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Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
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Two-Pore Channel Function Is Crucial for the Migration of Invasive Cancer Cells

Ong Nam Phuong Nguyen1, Christian Grimm2, Lina S Schneider1

  • 1Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University Munich, Munich, Germany.

Cancer Research
|January 22, 2017
PubMed

Insights

Two-pore channels (TPC) are potential targets for treating invasive cancers. Inhibiting TPC stops cancer cell migration and reduces metastasis by disrupting essential protein trafficking.

Area of Science:

  • Cell Biology
  • Oncology
  • Ion Channel Physiology

Background:

  • Metastatic invasion is a primary driver of cancer mortality.
  • Two-pore channels (TPC) are Ca2+-permeable cation channels in the endolysosomal system.
  • TPCs are sensitive to NAADP and PI(3,5)P2.

Purpose of the Study:

  • To investigate two-pore channels (TPC) as potential therapeutic targets for invasive cancers.
  • To determine the role of TPC in cancer cell migration and metastasis.

Main Methods:

  • In vitro assays to assess cancer cell migration.
  • Gene silencing and pharmacologic inhibition of TPC2 in mouse models.
  • Analysis of β1-integrin trafficking and leading edge formation in cancer cells.

Main Results:

  • Inhibition of TPC abrogated metastatic cancer cell migration in vitro.
  • Silencing or inhibiting TPC2 reduced lung metastasis in mice.
  • Disruption of TPC function led to β1-integrin accumulation in early endosomes, impairing leading edge formation and migration.

Conclusions:

  • TPCs are linked to cancer cell migration and metastasis.
  • TPCs represent a promising preclinical target for anti-metastatic cancer therapies.

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