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Updated: Aug 28, 2025

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
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Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth

Chunming Gu1,2, Wenhao Zhang1,2, Enze Yang1

  • 1School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China.

Oncogenesis
|September 15, 2022
PubMed

Insights

Nucleolin (NCL) directly interacts with Orai1, a key calcium channel, driving breast cancer cell proliferation. Blocking this interaction offers a potential therapeutic strategy for breast cancer by restoring calcium homeostasis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Calcium (Ca2+) acts as a crucial second messenger regulating diverse physiological functions.
  • Disruptions in intracellular calcium homeostasis are linked to various diseases, including cancer.
  • Orai1 channels are central to store-operated calcium entry (SOCE) and calcium homeostasis in non-excitable cells, with reported overexpression in breast cancer.

Purpose of the Study:

  • To identify novel interacting partners of Orai1 in breast cancer.
  • To elucidate the molecular mechanisms by which Orai1 contributes to breast cancer progression.
  • To explore the therapeutic potential of targeting the Orai1-interacting protein in breast cancer treatment.

Main Methods:

  • Co-immunoprecipitation assays to identify Orai1 interacting partners.
  • Western blotting and immunofluorescence to confirm protein interactions and localization.
  • In vitro and in vivo assays to assess the impact of NCL-Orai1 interaction on cell proliferation and calcium influx.
  • Peptide inhibition assays to block the NCL-Orai1 interaction.

Main Results:

  • Nucleolin (NCL) was identified as a novel interacting partner of Orai1.
  • The interaction between the C-terminus of NCL (NCL-CT) and the N-terminus of Orai1 (Orai1-NT) is essential for mediating calcium influx and breast cancer cell proliferation.
  • Blocking the NCL-Orai1 interaction with a synthesized Orai1 peptide significantly reduced intracellular calcium influx and suppressed breast cancer cell proliferation both in vitro and in vivo.

Conclusions:

  • NCL directly interacts with Orai1, representing a novel mechanism for Orai1 activation.
  • This interaction disrupts calcium homeostasis and promotes breast cancer cell proliferation.
  • Targeting the NCL-Orai1 interaction presents a promising therapeutic strategy for breast cancer.

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