SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling

Autor: Gwyndolen Harburg, Jennifer Compton, Wei Liu, Naomi Iwai, Shahrzad Zada, Rebecca Marlow, Phyllis Strickland, Yi Arial Zeng, Lindsay Hinck
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Stem Cell Reports, Vol 3, Iss 3, Pp 385-393 (2014)
Druh dokumentu: article
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2014.07.007
Popis: 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.
Databáze: Directory of Open Access Journals