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A balanced level of profilin-1 promotes stemness and tumor-initiating potential of breast cancer cells

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Bottcher,  Ralph
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Jiang, C., Ding, Z., Joy, M., Chakraborty, S., Kim, S. H., Bottcher, R., et al. (2017). A balanced level of profilin-1 promotes stemness and tumor-initiating potential of breast cancer cells. Cell Cycle, 16(24), 2366-2373. doi:10.1080/15384101.2017.1346759.


Cite as: https://hdl.handle.net/21.11116/0000-0000-B3FF-7
Abstract
Profilin-1 (Pfn1) is an important actin-regulatory protein that is downregulated in human breast cancer and when forcibly elevated, it suppresses the tumor-initiating ability of triple-negative breast cancer cells. In this study, we demonstrate that Pfn1 overexpression reduces the stem-like phenotype (a key biologic feature associated with higher tumor-initiating potential) of MDA-MB-231 (MDA-231) triple-negative breast cancer cells. Interestingly, the stem-like trait of MDA-231 cells is also attenuated upon depletion of Pfn1. A comparison of cancer stem cell gene (CSC) gene expression signatures between depleted and elevated conditions of Pfn1 further suggest that Pfn1 may be somehow involved in regulating the expression of a few CSC-related genes including MUC1, STAT3, FZD7, and ITGB1. Consistent with the reduced stem-like phenotype associated with loss-of-function of Pfn1, xenograft studies showed lower tumor-initiating frequency of Pfn1-depleted MDA-231 cells compared to their control counterparts. In MMTV: PyMT mouse model, homozygous but not heterozygous deletion of Pfn1 gene leads to severe genetic mosaicism and positive selection of Pfn1-proficient tumor cells further supporting the contention that a complete lack of Pfn1 is likely not conducive for efficient tumor initiation capability of breast cancer cells. In summary, these findings suggest that the maintenance of optimal stemness and tumor-initiating ability of breast cancer cells requires a balanced expression of Pfn1.