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

1 Citation (Scopus)

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

Fingerprint

Profilins
Breast Neoplasms
Neoplasms
Triple Negative Breast Neoplasms
Neoplastic Stem Cells
Genes
Phenotype
Mosaicism
Transcriptome
Heterografts
Actins
Down-Regulation

Keywords

  • Breast cancer
  • Profilin1
  • stemness
  • tumorigenicity

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Jiang, C., Ding, Z., Joy, M., Chakraborty, S., Kim, S. H., Bottcher, R., ... 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

A balanced level of profilin-1 promotes stemness and tumor-initiating potential of breast cancer cells. / Jiang, Chang; Ding, Zhijie; Joy, Marion; Chakraborty, Souvik; Kim, Su Hyeong; Bottcher, Ralph; Condeelis, John S.; Singh, Shivendra; Roy, Partha.

In: Cell Cycle, Vol. 16, No. 24, 17.12.2017, p. 2366-2373.

Research output: Contribution to journalArticle

Jiang, C, Ding, Z, Joy, M, Chakraborty, S, Kim, SH, Bottcher, R, Condeelis, JS, Singh, S & Roy, P 2017, 'A balanced level of profilin-1 promotes stemness and tumor-initiating potential of breast cancer cells', Cell Cycle, vol. 16, no. 24, pp. 2366-2373. https://doi.org/10.1080/15384101.2017.1346759
Jiang, Chang ; Ding, Zhijie ; Joy, Marion ; Chakraborty, Souvik ; Kim, Su Hyeong ; Bottcher, Ralph ; Condeelis, John S. ; Singh, Shivendra ; Roy, Partha. / A balanced level of profilin-1 promotes stemness and tumor-initiating potential of breast cancer cells. In: Cell Cycle. 2017 ; Vol. 16, No. 24. pp. 2366-2373.
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