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Updated: Sep 11, 2025

Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
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Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches

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STIM1-mediated calcium signalling in cancer: Its relation to tumour aggressiveness and therapeutic horizons

Songling Fang1, Yan Wang1, Zixian Huang1

  • 1Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|August 15, 2025
PubMed

Insights

Store-operated calcium entry (SOCE) regulated by STIM1 drives cancer metastasis and resistance. Targeting STIM1/Orai1 calcium channels offers a promising therapeutic strategy for various cancers, including oral cancer.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Calcium ions (Ca2+) are crucial regulators of tumor progression, influencing metastasis and therapy resistance.
  • STIM1-mediated store-operated calcium entry (SOCE) plays a pivotal role in these processes.
  • Dysregulated calcium signaling is increasingly recognized in various cancers, particularly oral cancer.

Purpose of the Study:

  • To review the role of STIM1 and SOCE-mediated calcium signaling in cancer progression.
  • To elucidate the mechanisms by which STIM1/Orai1 promotes epithelial-mesenchymal transition (EMT) and alters the tumor microenvironment.
  • To discuss the clinical implications of STIM1 as a prognostic biomarker and therapeutic target.

Main Methods:

  • Literature review focusing on STIM1, SOCE, and calcium signaling in cancer.
  • Analysis of mechanisms involving the STIM1/Orai1 complex, calmodulin (CaM), and downstream effectors.
  • Examination of clinical correlations between STIM1 overexpression and patient outcomes.

Main Results:

  • STIM1 overexpression correlates with advanced tumor stage, chemoresistance, and poor prognosis in cancer patients.
  • The STIM1/Orai1 complex activates CaM-dependent pathways promoting EMT, cytoskeletal remodeling, and an immunosuppressive tumor microenvironment.
  • Preclinical studies show CRAC channel inhibitors can suppress tumor growth.

Conclusions:

  • STIM1 is a significant factor in cancer metastasis and therapy resistance, acting as both a prognostic biomarker and therapeutic target.
  • Targeting STIM1/Orai1-mediated calcium signaling presents a viable therapeutic strategy for cancer treatment.
  • Further research integrating advanced technologies is needed to overcome challenges and accelerate clinical translation of calcium signaling modulators.
Keywords:
Calcium signallingSOCE (store-operated calcium entry)STIM1Tumour metastasiscancer therapy

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