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CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo
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 differ...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986630/ https://www.ncbi.nlm.nih.gov/pubmed/24749068 http://dx.doi.org/10.1016/j.stemcr.2014.02.010 |
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author | Spike, Benjamin T. Kelber, Jonathan A. Booker, Evan Kalathur, Madhuri Rodewald, Rose Lipianskaya, Julia La, Justin He, Marielle Wright, Tracy Klemke, Richard Wahl, Geoffrey M. Gray, Peter C. |
author_facet | Spike, Benjamin T. Kelber, Jonathan A. Booker, Evan Kalathur, Madhuri Rodewald, Rose Lipianskaya, Julia La, Justin He, Marielle Wright, Tracy Klemke, Richard Wahl, Geoffrey M. Gray, Peter C. |
author_sort | Spike, Benjamin T. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3986630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-39866302014-04-18 CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo Spike, Benjamin T. Kelber, Jonathan A. Booker, Evan Kalathur, Madhuri Rodewald, Rose Lipianskaya, Julia La, Justin He, Marielle Wright, Tracy Klemke, Richard Wahl, Geoffrey M. Gray, Peter C. Stem Cell Reports Report 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. Elsevier 2014-04-03 /pmc/articles/PMC3986630/ /pubmed/24749068 http://dx.doi.org/10.1016/j.stemcr.2014.02.010 Text en © 2014 The Authors https://creativecommons.org/licenses/by-nc-nd/3.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License (https://creativecommons.org/licenses/by-nc-nd/3.0/) . |
spellingShingle | Report Spike, Benjamin T. Kelber, Jonathan A. Booker, Evan Kalathur, Madhuri Rodewald, Rose Lipianskaya, Julia La, Justin He, Marielle Wright, Tracy Klemke, Richard Wahl, Geoffrey M. Gray, Peter C. CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo |
title | CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo |
title_full | CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo |
title_fullStr | CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo |
title_full_unstemmed | CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo |
title_short | CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo |
title_sort | cripto/grp78 signaling maintains fetal and adult mammary stem cells ex vivo |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986630/ https://www.ncbi.nlm.nih.gov/pubmed/24749068 http://dx.doi.org/10.1016/j.stemcr.2014.02.010 |
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