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Regulator of calcineurin 1 modulates cancer cell migration in vitro

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Abstract

Metastasis suppressors and other regulators of cell motility play an important role in tumor invasion and metastases. We previously identified that activation of the G protein coupled receptor 54 (GPR54) by the metastasis suppressor metastin inhibits cell migration in association with overexpression of Regulator of calcineurin 1 (RCAN1), an endogenous regulator of calcineurin. Calcineurin inhibitors also blocked cell migration in vitro and RCAN1 protein levels were reduced in nodal metastases in thyroid cancer. The purpose of the current study was to determine directly if RCAN1 functions as a motility suppressor in vitro. Several cancer cell lines derived from different cancer types with different motility rates were evaluated for RCAN1 expression levels. Using these systems we determined that reduction of endogenous RCAN1 using siRNA resulted in an increase in cancer cell motility while expression of exogenous RCAN1 reduced cell motility. In one cell line with a high migratory rate, the stability of exogenously expressed RCAN1 protein was reduced and was rescued by treatment with a proteasome inhibitor. Finally, overexpression of RCAN1 was associated with an increase in cell adhesion to collagen IV and reduced calcineurin activity. In summary, we have demonstrated that the expression of exogenous RCAN1 reduces migration and alters adhesion; and that the loss of endogenous RCAN1 leads to an increase in migration in the examined cancer cell lines. These results are consistent with a regulatory role for RCAN1 in cancer cell motility in vitro.

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Abbreviations

RCAN1:

Regulator of calcineurin 1

NFAT:

Nuclear factor of activated T-cells

FTC:

Follicular thyroid cancer

GPR54:

G protein coupled receptor 54

PBS:

Phosphate-buffered saline

TBS:

Tris-buffered saline

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Acknowledgments

This work was supported by grants 1R21 CA111461 and 1R01 CA102572 to MDR from NIH.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University College of Medicine and Arthur G. James Comprehensive Cancer Center, 445D McCampbell Hall, 1581 Dodd Drive, Columbus, OH, 43210, USA

    Allan V. Espinosa, Motoo Shinohara, Leonardo M. Porchia, Yun Jae Chung, Samantha McCarty, Motoyasu Saji & Matthew D. Ringel

  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea

    Yun Jae Chung

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  1. Allan V. Espinosa
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  2. Motoo Shinohara
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  3. Leonardo M. Porchia
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  4. Yun Jae Chung
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  6. Motoyasu Saji
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Correspondence to Matthew D. Ringel.

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Espinosa, A.V., Shinohara, M., Porchia, L.M. et al. Regulator of calcineurin 1 modulates cancer cell migration in vitro. Clin Exp Metastasis 26, 517–526 (2009). https://doi.org/10.1007/s10585-009-9251-1

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  • DOI: https://doi.org/10.1007/s10585-009-9251-1

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