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

Chang Jiang, Zhijie Ding, Marion Joy, Souvik Chakraborty, Su Hyeong Kim, Ralph Bottcher, John S. Condeelis, Shivendra Singh, Partha Roy

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2366-2373
Number of pages8
JournalCell Cycle
Volume16
Issue number24
DOIs
StatePublished - Dec 17 2017

Keywords

  • Breast cancer
  • Profilin1
  • stemness
  • tumorigenicity

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

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