AKT Regulation of ORAI1-Mediated Calcium Influx in Breast Cancer Cells

Alice Hui Li Bong1, Trinh Hua1, Choon Leng So1

  • 1School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia.

Cancers
|October 14, 2022
PubMed

Insights

Silencing PTEN or activating AKT increases calcium influx in basal breast cancer cells. This calcium influx is mediated by AKT2 and the ORAI1 channel, suggesting ORAI1 as a potential therapeutic target.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Breast cancer cells frequently display dysregulated AKT and calcium signaling pathways.
  • The precise interplay between these two critical signaling cascades remains largely undefined.

Purpose of the Study:

  • To elucidate the association between PTEN, AKT phosphorylation, and calcium signaling in basal breast cancer.
  • To investigate the role of specific AKT isoforms and calcium channels in this crosstalk.

Main Methods:

  • Utilized siRNA and CRISPR/Cas9 gene silencing techniques.
  • Employed pharmacological AKT activator SC79 and specific inhibitors.
  • Analyzed calcium influx in MDA-MB-231 basal breast cancer cells.

Main Results:

  • PTEN silencing and SC79 treatment both enhanced AKT phosphorylation and calcium influx.
  • Increased calcium influx was dependent on AKT2, not AKT1.
  • Silencing ORAI1 suppressed the SC79-induced calcium influx.

Conclusions:

  • PTEN/AKT signaling positively regulates calcium influx in basal breast cancer cells.
  • AKT2 and the ORAI1 channel are key mediators of this crosstalk.
  • ORAI1 represents a potential therapeutic target for breast cancers with aberrant AKT activation.

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