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Review
. 2025 May;87(2):182-195.
doi: 10.18999/nagjms.87.2.182.

Calcineurin in cancer signaling networks

Honoka Haba  1 , Shoma Tsubota  1 , Midori Shimada  1
Affiliations
Review

Calcineurin in cancer signaling networks

Honoka Haba et al. Nagoya J Med Sci. 2025 May.

Abstract

Calcium/calcineurin/nuclear factor of activated T-cell signaling is a vital regulator of the development and function of immune, nervous, cardiovascular, and musculoskeletal systems. The dysregulation of calcineurin activity has been implicated in various pathological conditions, including certain cancers, cardiac hypertrophy, and neurodegenerative disorders. Calcineurin is highly expressed in certain cancers and stabilizes and activates factors that promote cancer cell proliferation. Research has shown that protein dephosphorylation by calcineurin contributes to tumor formation and progression. Thus, elucidating molecular mechanisms of calcineurin-mediated tumorigenesis and tumor cell growth and targeting signaling pathways downstream of calcineurin may lead to new cancer therapies. This study reviewed the multiple roles of calcineurin in cell cycle progression and its potential as a target for cancer treatment.

Keywords: calcineurin; calcium; cell proliferation; dephosphorylation; prognosis in cancer.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Schematic illustration of the structure of CnA and CnB subunits In mammals, three genes encode CnA (CnAα, CnAβ, and CnAγ), and CnAβ contains two splice variants (CnAβ1 and CnAβ2). CnA: calcineurin A CnB: calcineurin B
Fig. 2
Fig. 2
Calcineurin signaling pathway to activate cancer cell proliferation Increased cytosolic Ca2+ concentrations, for example, by activating Ca2+ channels, activate calmodulin, which in turn activates calcineurin composed of CnA and CnB. Activated calcineurin dephosphorylates and regulates NFAT transcription factors and other targets. Cyclosporine and FK506 are calcineurin inhibitors. Factors important in the regulation of calcineurin activity are shown in the figure. Calcineurin stabilizes, transcriptionally activates, and alters the localization of factors that promote and activate cell proliferation, promoting cancer cell proliferation. AKAP: A-kinase anchoring protein CnA: calcineurin A CnB: calcineurin B EGFR: epidermal growth factor receptor ERα: estrogen receptor-α NFAT: nuclear factor of activated T cell RCAN: regulator of calcineurin
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