SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling
| Autor: | Shahrzad Zada, Lindsay Hinck, Rebecca Marlow, Jennifer E. Compton, Naomi Iwai, Yi Arial Zeng, Wei Liu, Gwyndolen Harburg, Phyllis Strickland |
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| Rok vydání: | 2014 |
| Předmět: |
Beta-catenin
1.1 Normal biological development and functioning Cellular differentiation Clinical Sciences Morphogenesis Nerve Tissue Proteins Regenerative Medicine Biochemistry Mice Stem Cell Research - Nonembryonic - Human Immunologic Report Receptors Genetics SLIT2 Animals Humans Receptors Immunologic Mammary Glands Human lcsh:QH301-705.5 Cellular Senescence lcsh:R5-920 biology Stem Cells Wnt signaling pathway Cell Biology Stem Cell Research Mammary Glands Cell biology Wnt Proteins lcsh:Biology (General) Cell Aging biology.protein Intercellular Signaling Peptides and Proteins Stem Cell Research - Nonembryonic - Non-Human Biochemistry and Cell Biology Stem cell Signal transduction lcsh:Medicine (General) Gene Deletion Human Signal Transduction Developmental Biology Adult stem cell |
| Zdroj: | Stem Cell Reports, Vol 3, Iss 3, Pp 385-393 (2014) Stem Cell Reports Stem cell reports, vol 3, iss 3 Harburg, G; Compton, J; Liu, W; Iwai, N; Zada, S; Marlow, R; et al.(2014). SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling. Stem Cell Reports, 3(3), 385-393. doi: 10.1016/j.stemcr.2014.07.007. UC Office of the President: Research Grants Program Office (RGPO). Retrieved from: http://www.escholarship.org/uc/item/6p50215s Harburg, G; Compton, J; Liu, W; Iwai, N; Zada, S; Marlow, R; et al.(2014). SLIT/ROBO2 signaling promotes mammary stem cell senescence by inhibiting wnt signaling. Stem Cell Reports, 3(3), 385-393. doi: 10.1016/j.stemcr.2014.07.007. UC Santa Cruz: Retrieved from: http://www.escholarship.org/uc/item/84q569vd Stem Cell Reports, vol 3, iss 3 |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2014.07.007 |
| Popis: | Summary 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 p16INK4a, 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. Graphical Abstract Highlights • SLIT2 opposes WNT signaling to act as a mammary stem cell nonrenewal factor • SLIT/ROBO2 signaling increases p16INK4a expression, promoting cellular senescence • Loss of SLIT/ROBO2 signaling enhances mammary gland serial transplantability In this article, Hinck and colleagues show that SLIT2 restricts stem cell renewal by signaling through ROBO2 and opposing WNT signaling. This results in increased expression of p16INK4a, promoting cellular senescence. |
| Databáze: | OpenAIRE |
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