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Updated: Mar 11, 2026
Fluorescence-based Measurement of Store-operated Calcium Entry in Live Cells: from Cultured Cancer Cell to Skeletal Muscle Fiber
Published on: February 13, 2012
Context-dependent dysregulation of store-operated calcium channels in head and neck squamous cell carcinoma
Heba Ghozlan1, Saja Al-Malahmeh1, Othman Al-Shboul1
1Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
Abstract:
Store-operated calcium entry (SOCE), mediated by ORAI1-3 calcium channels and stromal interaction molecules STIM1 and STIM2, is increasingly recognized as a regulator of cancer progression. However, its role in head and neck squamous cell carcinoma (HNSCC) and its relationship with major oncogenic pathways remain poorly defined. Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) were analyzed to profile isoform-specific ORAI1-3 and STIM1-2 expression across HNSCC subtypes and oncogenic contexts. In parallel, the effects of pharmacologic SOCE inhibition with 2-aminoethoxydiphenyl borate (2-APB) were evaluated in FaDu (epidermal growth factor receptor [EGFR]-high, PIK3CA-wild-type) and Detroit-562 (metastatic, PIK3CA-mutant) cells by assessing viability, migration, and clonogenic survival. TCGA analysis revealed a context-dependent SOCE expression profile. ORAI1-3 and STIM2 were broadly upregulated in tumors, while STIM1 was significantly downregulated, particularly in advanced and basaloid subtypes. PIK3CA mutations, especially the H1047R hotspot, were associated with higher STIM1 expression, whereas EGFR expression correlated positively with STIM1/2 but negatively with ORAI1/3. In vitro, Detroit-562 cells expressed higher levels of SOCE components and showed greater sensitivity to SOCE inhibition, with marked reductions in viability, migration, and clonogenic capacity. FaDu cells, despite higher EGFR expression, exhibited lower SOCE gene expression and relative resistance to 2-APB, which suggests reduced dependence on SOCE-mediated signaling. These findings suggest that SOCE components are transcriptionally dysregulated in HNSCC and may represent a context-dependent therapeutic vulnerability, particularly in PIK3CA-mutant tumors. Validation in additional preclinical models, patient-derived xenografts, and clinical specimens is required to establish SOCE as a biomarker and therapeutic target in HNSCC.
Insights
Store-operated calcium entry (SOCE) is dysregulated in head and neck squamous cell carcinoma (HNSCC). SOCE inhibition impacts cancer cell viability and migration, suggesting it
Area of Science:
- Oncology
- Molecular Biology
- Calcium Signaling
Background:
- Store-operated calcium entry (SOCE) is a critical calcium influx mechanism implicated in cancer progression.
- The specific role and therapeutic potential of SOCE in head and neck squamous cell carcinoma (HNSCC) remain largely undefined.
- Understanding SOCE's interaction with oncogenic pathways like EGFR and PIK3CA is crucial for HNSCC treatment strategies.
Purpose of the Study:
- To investigate the expression profile of SOCE components (ORAI1-3, STIM1-2) in HNSCC.
- To explore the relationship between SOCE gene expression and major oncogenic pathways (EGFR, PIK3CA) in HNSCC.
- To evaluate the therapeutic potential of SOCE inhibition in HNSCC cell lines.
Main Methods:
- Analysis of transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) for HNSCC.
- Profiling of ORAI1-3 and STIM1-2 expression across HNSCC subtypes and oncogenic contexts.
- In vitro assessment of SOCE inhibition using 2-aminoethoxydiphenyl borate (2-APB) in FaDu and Detroit-562 HNSCC cell lines, measuring viability, migration, and clonogenic survival.
Main Results:
- SOCE components showed context-dependent expression in HNSCC; ORAI1-3 and STIM2 were upregulated, while STIM1 was downregulated in advanced/basaloid subtypes.
- PIK3CA mutations correlated with higher STIM1 expression, and EGFR expression showed mixed correlations with SOCE components.
- Detroit-562 cells (PIK3CA-mutant) exhibited higher SOCE component expression and greater sensitivity to 2-APB, showing reduced viability, migration, and clonogenic survival compared to FaDu cells (EGFR-high).
Conclusions:
- SOCE components are transcriptionally dysregulated in HNSCC, indicating a context-dependent role.
- SOCE inhibition demonstrates therapeutic vulnerability, particularly in PIK3CA-mutant HNSCC.
- Further validation in preclinical models and clinical specimens is necessary to establish SOCE as a biomarker and therapeutic target in HNSCC.
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