Abstract
Galectin-3 (Gal-3) is a multifunctional protein involved in cancer through regulation of cell adhesion, cell growth, apoptosis and metastasis, while p21 (Cip1/WAF1) is a negative regulator of the cell cycle, involved in apoptosis, transcription, DNA repair and metastasis. The results presented here demonstrate for the first time that the level of Gal-3 protein is associated with the level of p21 protein expression in human prostate cancer cells and the effects of Gal-3 on cell growth and apoptosis were reversed by modulating p21 expression level. Furthermore, Gal-3 regulates p21 expression at the post-translational level by stabilizing p21 protein via the carbohydrate-recognition domain. This is the first report suggesting a molecular function not yet described for Gal-3 as the regulator of p21 protein stability. This study provides a unique insight into the relationship of these two molecules during prostate cancer progression, and may provide a novel therapeutic target.
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Acknowledgements
We thank Dr Reuben Lotan for providing Gal-3-transfected LNCaP clones. This study was supported by the National Institutes of Health grant R37CA46120-19 (A Raz) and the American Cancer Society grant 11-053-01-IRG (V Balan).
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Wang, Y., Balan, V., Kho, D. et al. Galectin-3 regulates p21 stability in human prostate cancer cells. Oncogene 32, 5058–5065 (2013). https://doi.org/10.1038/onc.2012.528
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DOI: https://doi.org/10.1038/onc.2012.528
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