Telephone: +39-011-670-6422; Fax: +39-011-670-6432
Tissue-Specific Stem Cells
Article first published online: 5 JUL 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 7, pages 1422–1433, July 2013
How to Cite
Tornillo, G., Elia, A. R., Castellano, I., Spadaro, M., Bernabei, P., Bisaro, B., Camacho-Leal, M. d. P., Pincini, A., Provero, P., Sapino, A., Turco, E., Defilippi, P. and Cabodi, S. (2013), p130Cas alters the differentiation potential of mammary luminal progenitors by deregulating c-Kit activity. STEM CELLS, 31: 1422–1433. doi: 10.1002/stem.1403
Author contributions: G.T.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; A.R.E., M.S., P.B., B.B., A.P., and E.T.: collection and/or assembly of data; I.C. and A.S.: provision of study material or patients and data analysis and interpretation; P.P., M.d.P.C.-L., and P.D.: data analysis and interpretation; S.C.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
first published online in STEM CELLS EXPRESS April 17, 2013.
- Issue published online: 5 JUL 2013
- Article first published online: 5 JUL 2013
- Accepted manuscript online: 17 APR 2013 06:23AM EST
- Manuscript Accepted: 14 MAR 2013
- Manuscript Revised: 5 MAR 2013
- Manuscript Received: 7 NOV 2012
- AIRC. Grant Numbers: IG2008, IG2011
- Mammary luminal progenitor;
- Basal-like breast cancer
It has recently been proposed that defective differentiation of mammary luminal progenitors predisposes to basal-like breast cancer. However, the molecular and cellular mechanisms involved are still unclear. Here, we describe that the adaptor protein p130Cas is a crucial regulator of mouse mammary epithelial cell (MMEC) differentiation. Using a transgenic mouse model, we show that forced p130Cas overexpression in the luminal progenitor cell compartment results in the expansion of luminal cells, which aberrantly display basal cell features and reduced differentiation in response to lactogenic stimuli. Interestingly, MMECs overexpressing p130Cas exhibit hyperactivation of the tyrosine kinase receptor c-Kit. In addition, we demonstrate that the constitutive c-Kit activation alone mimics p130Cas overexpression, whereas c-Kit downregulation is sufficient to re-establish proper differentiation of p130Cas overexpressing cells. Overall, our data indicate that high levels of p130Cas, via abnormal c-Kit activation, promote mammary luminal cell plasticity, thus providing the conditions for the development of basal-like breast cancer. Consistently, p130Cas is overexpressed in human triple-negative breast cancer, further suggesting that p130Cas upregulation may be a priming event for the onset of basal-like breast cancer. STEM Cells2013;31:1422–1433