Show simple item record

dc.contributor.authorPelissier, Fannyen_US
dc.contributor.authorGarbe, James C.en_US
dc.contributor.authorAnanthanarayanan, Badriprasaden_US
dc.contributor.authorMiyano, Masaruen_US
dc.contributor.authorLin, ChunHanen_US
dc.contributor.authorJokela, Tiinaen_US
dc.contributor.authorKumar, Sanjayen_US
dc.contributor.authorStampfer, Martha R.en_US
dc.contributor.authorLorens, Jamesen_US
dc.contributor.authorLaBarge, Mark A.en_US
dc.description.abstractDysfunctional progenitor and luminal cells with acquired basal cell properties accumulate during human mammary epithelial aging for reasons not understood. Multipotent progenitors from women aged <30 years were exposed to a physiologically relevant range of matrix elastic modulus (stiffness). Increased stiffness causes a differentiation bias towards myoepithelial cells while reducing production of luminal cells and progenitor maintenance. Lineage representation in progenitors from women >55 years is unaffected by physiological stiffness changes. Efficient activation of Hippo pathway transducers YAP and TAZ is required for the modulus-dependent myoepithelial/ basal bias in younger progenitors. In older progenitors, YAP and TAZ are activated only when stressed with extraphysiologically stiff matrices, which bias differentiation towards luminal-like phenotypes. In vivo YAP is primarily active in myoepithelia of younger breasts, but localization and activity increases in luminal cells with age. Thus, aging phenotypes of mammary epithelia may arise partly because alterations in Hippo pathway activation impair microenvironment-directed differentiation and lineage specificity.en_US
dc.relation.ispartof<a href="" target="_blank">The Role of Age in Cellular Responses to Microenvironmental Cues as a Breast Cancer Susceptibility Factor</a>
dc.rightsAttribution-NonCommercial-NoDerivs CC BY-NC-NDeng
dc.titleAge-Related Dysfunction in Mechanotransduction Impairs Differentiation of Human Mammary Epithelial Progenitorsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2014 The Authors
dc.source.journalCell reports

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivs CC BY-NC-ND
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs CC BY-NC-ND