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Calcium Homeostasis Machinery in the Human Uterus—A Potential Therapeutic Target in Endometrial Cancer

Year: 2025

Type: article

Abstract: Endometrial cancer is one of the most common malignancies of the female reproductive system, with incidence rising globally due to population ageing and life-style-related risk factors. Calcium (Ca2+) is a ubiquitous second messenger regulating diverse physiological processes, and its dysregulation has been increasingly implicated in carcinogenesis, including endometrial. Altered expression and function of Ca2+ channels, pumps, exchangers, and binding proteins disrupt the finely tuned balance of Ca2+ influx, efflux, and intracellular storage, leading to aberrant signalling that promotes tumour proliferation, migration, survival, and metastasis. This review summarises current knowledge on the molecular “Ca2+ toolkit” in the human uterus, highlighting the role of voltage-gated calcium channels (VGCCs), transient receptor potential (TRP) channels, store-operated calcium entry (SOCE) components, Na+/Ca2+ exchangers, purinergic receptors, P-type ATPases (SERCA, SPCA, PMCA), ryanodine (RyR) and inositol 1,4,5-trisphosphate (IP3R) receptors, and mitochondrial Ca2+ uniporter (MCU) complexes in endometrial cancer progression. Multiple Ca2+-handling proteins, including CACNA1D, CACNA2D1, TRPV4, TRPV1, TRPM4, MCU, and RyR1, exhibit cancer-associated overexpression or functional changes, correlating with poor prognosis and aggressive disease features. Emerging evidence supports the therapeutic potential of targeting Ca2+ homeostasis using small-molecule inhibitors, ion channel modulators or gene-silencing strategies. These interventions may restore Ca2+ balance, induce apoptosis or autophagy, and suppress metastatic behaviour. While no clinical trials have yet explicitly focused on Ca2+ modulation in endometrial cancer, the diversity of dysregulated Ca2+ pathways offers a rich landscape for novel therapeutic strategies. Targeting key components of the Ca2+ signalling network holds promise for improving outcomes in endometrial cancer.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms262110253

Author: Piotr K. Zakrzewski

Institution: Medical University of Lodz

Language: English

Topic: Ion Channels and Receptors

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499