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Stem Cell Reports. 2014 Apr 3;2(4):427-39. doi: 10.1016/j.stemcr.2014.02.010. eCollection 2014 Apr 8.

CRIPTO/GRP78 signaling maintains fetal and adult mammary stem cells ex vivo.

Author information

1
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Department of Pathology, University of California, San Diego, La Jolla, CA 92037, USA.
3
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Abstract

Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78 as regulators of stem cell behavior in isolated fetal and adult mammary epithelial cells. We develop a CRIPTO antagonist that promotes differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By contrast, CRIPTO treatment maintains the stem cell phenotype in these cultures and yields colonies with enhanced mammary gland reconstitution capacity. Surface expression of GRP78 marks CRIPTO-responsive, stem cell-enriched fetal and adult mammary epithelial cells, and deletion of GRP78 from adult mammary epithelial cells blocks their mammary gland reconstitution potential. Together, these findings identify the CRIPTO/GRP78 pathway as a developmentally conserved regulator of fetal and adult mammary stem cell behavior ex vivo, with implications for the stem-like cells found in many cancers.

PMID:
24749068
PMCID:
PMC3986630
DOI:
10.1016/j.stemcr.2014.02.010
[Indexed for MEDLINE]
Free PMC Article

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