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Targeting Stim and Orai Proteins as an Alternative Approach in Anticancer Therapy
Francesco Moccia1, Estella Zuccolo, Valentina Poletto
1Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Forlanini 6, 27100, Pavia, Italy. francesco.moccia@unipv.it.
Abstract:
An increase in intracellular Ca2+ concentration plays a key role in the establishment of many cancer hallmarks, including aberrant proliferation, migration, invasion, resistance to apoptosis and angiogenesis. The dysregulation of Ca2+ entry is one of the most subtle mechanisms by which cancer cells overwhelm their normal counterparts and gain the adaptive advantages that result in tumour growth, vascularisation and dissemination throughout the organism. Both constitutive and agonist-induced Ca2+ influx may be mediated by store-dependent as well as store-independent Ca2+ entry routes. A growing body of evidences have shown that different isoforms of Stromal Interaction Molecules (Stim1) and Orai proteins, i.e. Stim1, Stim2, Orai1 and Orai3, underlie both pathways in cancer cells. The alteration in either the expression or the activity of Stim and Orai proteins has been linked to the onset and maintenance of tumour phenotype in many solid malignancies, including prostate, breast, kidney, esophageal, skin, brain, colorectal, lung and liver cancers. Herein, we survey the existing data in support of Stim and Orai involvement in tumourigenesis and provide the rationale to target them in cancer patients. Besides, we summarize the most recent advances in the identification of novel pharmacological tools that could be successfully used in clinical therapy.
Insights
Altered calcium (Ca2+) signaling via Stromal Interaction Molecules (Stim) and Orai proteins drives cancer progression. Targeting these proteins offers a promising therapeutic strategy for various solid tumors.
Area of Science:
- Cellular Biology
- Molecular Oncology
- Cancer Research
Background:
- Intracellular Ca2+ concentration is crucial for cancer hallmarks like proliferation, migration, invasion, and angiogenesis.
- Dysregulation of Ca2+ entry provides cancer cells with adaptive advantages for tumor growth and metastasis.
- Both store-dependent and store-independent Ca2+ entry pathways are implicated in cancer.
Purpose of the Study:
- To review the role of Stromal Interaction Molecules (Stim) and Orai proteins in cancer.
- To provide evidence for targeting Stim and Orai proteins in cancer therapy.
- To summarize recent advancements in pharmacological tools for targeting these pathways.
Main Methods:
- Literature review of existing data on Stim and Orai proteins in cancer.
- Analysis of the involvement of Stim1, Stim2, Orai1, and Orai3 in cancer cell pathways.
- Survey of current research on pharmacological interventions targeting Stim and Orai proteins.
Main Results:
- Stim and Orai proteins (Stim1, Stim2, Orai1, Orai3) mediate Ca2+ entry in cancer cells.
- Altered expression or activity of Stim and Orai proteins is linked to tumor phenotype in multiple solid cancers.
- These proteins are involved in cancer hallmarks including proliferation, migration, invasion, and angiogenesis.
Conclusions:
- Stim and Orai proteins are key players in cancer development and progression.
- Targeting Stim and Orai proteins presents a viable therapeutic strategy for cancer patients.
- Novel pharmacological agents targeting these pathways show potential for clinical application.
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