Related Experiment Video

Updated: Sep 20, 2025

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

1.7K

ORAI1-Regulated Gene Expression in Breast Cancer Cells: Roles for STIM1 Binding, Calcium Influx and Transcription

Mélanie Robitaille1, Shao Ming Chan1, Amelia A Peters1

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

International Journal of Molecular Sciences
|June 10, 2022
PubMed

Insights

Store-operated calcium entry (SOCE) protein ORAI1 regulates gene transcription in basal breast cancer cells. ORAI1 influences cancer progression by controlling gene expression, impacting breast cancer development.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Calcium Signaling

Background:

  • Calcium homeostasis is altered in breast cancers, with store-operated calcium entry (SOCE) playing a key role.
  • ORAI1, a critical component of SOCE, is upregulated in basal breast cancer cells.
  • The specific role of ORAI1 in regulating gene transcription in this subtype remains largely unknown.

Purpose of the Study:

  • To investigate the function of ORAI1 in gene transcriptional regulation in basal breast cancer cells.
  • To determine if ORAI1's role in transcription is dependent on its pore function and interaction with STIM1.
  • To elucidate ORAI1's contribution to breast cancer progression via gene expression modulation.

Main Methods:

  • CRISPR-Cas9 gene editing was employed to disrupt ORAI1 expression in MDA-MB-231 and MDA-MB-468 basal breast cancer cell lines.
  • ORAI1 wild-type and mutant variants were reintroduced into knockout cells to assess functional roles.
  • Transcriptional changes were analyzed in response to ORAI1 manipulation and SOCE activation.

Main Results:

  • In MDA-MB-231 cells, ORAI1 regulated *PTGS2* transcription independently of calcium store depletion, contingent on ORAI1 pore function and STIM1 binding.
  • In MDA-MB-468 cells, SOCE activation led to ORAI1-dependent increases in *IL6* transcription, also requiring ORAI1 pore function and STIM1 binding.
  • ORAI1-mediated *IL6* transcriptional changes were associated with NFAT1 translocation.

Conclusions:

  • ORAI1 plays a significant role in regulating gene transcription (*PTGS2* and *IL6*) in basal breast cancer cells.
  • This transcriptional regulation is dependent on ORAI1's pore activity and STIM1 interaction.
  • The findings suggest ORAI1 contributes to breast cancer progression through modulation of gene expression, highlighting its potential as a therapeutic target.
Keywords:
ORAI1breast cancercalcium signaling

More Related Videos

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement10:45

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement

Published on: July 26, 2017

10.3K
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

10.6K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.0K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.3K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.6K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
14.0K