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SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling
WNT signaling stimulates the self-renewal of many types of adult stem cells, including mammary stem cells (MaSCs), but mechanisms that limit this activity are poorly understood. Here, we demonstrate that SLIT2 restricts stem cell renewal by signaling through ROBO2 in a subset of basal cells to negat...
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/PMC4266005/ https://www.ncbi.nlm.nih.gov/pubmed/25241737 http://dx.doi.org/10.1016/j.stemcr.2014.07.007 |
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author | Harburg, Gwyndolen Compton, Jennifer Liu, Wei Iwai, Naomi Zada, Shahrzad Marlow, Rebecca Strickland, Phyllis Zeng, Yi Arial Hinck, Lindsay |
author_facet | Harburg, Gwyndolen Compton, Jennifer Liu, Wei Iwai, Naomi Zada, Shahrzad Marlow, Rebecca Strickland, Phyllis Zeng, Yi Arial Hinck, Lindsay |
author_sort | Harburg, Gwyndolen |
collection | PubMed |
description | WNT signaling stimulates the self-renewal of many types of adult stem cells, including mammary stem cells (MaSCs), but mechanisms that limit this activity are poorly understood. Here, we demonstrate that SLIT2 restricts stem cell renewal by signaling through ROBO2 in a subset of basal cells to negatively regulate WNT signaling. The absence of SLIT/ROBO2 signaling leads to increased levels of nuclear β-catenin. Robo2 loss does not increase the number of stem cells; instead, stem cell renewal is enhanced in the absence of SLIT/ROBO2 signaling. This is due to repressed expression of p16(INK4a), which, in turn, delays MaSC senescence. Together, our studies support a model in which SLITs restrict the expansion of MaSCs by countering the activity of WNTs and limiting self-renewal. |
format | Online Article Text |
id | pubmed-4266005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-42660052014-12-16 SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling Harburg, Gwyndolen Compton, Jennifer Liu, Wei Iwai, Naomi Zada, Shahrzad Marlow, Rebecca Strickland, Phyllis Zeng, Yi Arial Hinck, Lindsay Stem Cell Reports Report WNT signaling stimulates the self-renewal of many types of adult stem cells, including mammary stem cells (MaSCs), but mechanisms that limit this activity are poorly understood. Here, we demonstrate that SLIT2 restricts stem cell renewal by signaling through ROBO2 in a subset of basal cells to negatively regulate WNT signaling. The absence of SLIT/ROBO2 signaling leads to increased levels of nuclear β-catenin. Robo2 loss does not increase the number of stem cells; instead, stem cell renewal is enhanced in the absence of SLIT/ROBO2 signaling. This is due to repressed expression of p16(INK4a), which, in turn, delays MaSC senescence. Together, our studies support a model in which SLITs restrict the expansion of MaSCs by countering the activity of WNTs and limiting self-renewal. Elsevier 2014-08-28 /pmc/articles/PMC4266005/ /pubmed/25241737 http://dx.doi.org/10.1016/j.stemcr.2014.07.007 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Report Harburg, Gwyndolen Compton, Jennifer Liu, Wei Iwai, Naomi Zada, Shahrzad Marlow, Rebecca Strickland, Phyllis Zeng, Yi Arial Hinck, Lindsay SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling |
title | SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling |
title_full | SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling |
title_fullStr | SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling |
title_full_unstemmed | SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling |
title_short | SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling |
title_sort | slit/robo2 signaling promotes mammary stem cell senescence by inhibiting wnt signaling |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266005/ https://www.ncbi.nlm.nih.gov/pubmed/25241737 http://dx.doi.org/10.1016/j.stemcr.2014.07.007 |
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