The Hippo Transducer TAZ Confers Cancer Stem Cell-Related Traits on Breast Cancer Cells
Cette étude identifie le rôle joué par TAZ, une protéine de la voie de signalisation Hippo, dans la capacité des cellules souches de cancer du sein à se renouveler et à favoriser la transition épithélio-mésenchymateuse
Cancer stem cells (CSCs) are proposed to drive tumor initiation and progression. Yet, our understanding of the cellular and molecular mechanisms that underlie CSC properties is limited. Here we show that the activity of TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in breast CSCs. TAZ protein levels and activity are elevated in prospective CSCs and in poorly differentiated human tumors and have prognostic value. Gain of TAZ endows self-renewal capacity to non-CSCs. In epithelial cells, TAZ forms a complex with the cell-polarity determinant Scribble, and loss of Scribble or induction of the epithelial-mesenchymal transition (EMT) disrupts the inhibitory association of TAZ with the core Hippo kinases MST and LATS. This study links the CSC concept to the Hippo pathway in breast cancer and reveals a mechanistic basis of the control of Hippo kinases by cell polarity. º TAZ activity is associated with tumor differentiation and prognosis º Expression of TAZ endows self-renewal and tumor-initiation capacities º EMT induces TAZ activity via loss of cell-polarity factor Scribble º Scribble inhibits TAZ by activating the Hippo pathway in breast cancer The Hippo pathway effector TAZ promotes cancer stem cell-like traits such as self-renewal and tumorigenicity and links these with the loss of cell polarity and the epithelial-mesenchymal transition.