On the nature and plasticity of cancer stem cell phenotype

Cancer Stem Cells (CSCs) are proposed to drive tumor initiation and progression. But what is "making" a cancer cell a cancer stem cell? In fact, our understanding of the cellular and molecular mechanisms that underlie CSC phenomenon is limited. We discovered that TAZ, a transducer of the Hippo pathway, sustains self-renewal and tumor-initiation capacities of breast CSCs (Cordenonsi et al., Cell 2011). TAZ protein levels and activity are elevated in prospective CSCs and in poorly differentiated human tumors; and TAZ/YAP activity identifies tumors that will form metastases and with poor prognosis. Gain-of-TAZ endows self-renewal capacity to non-CSCs, and confers them capacity to resist to chemotherapy. TAZ is downstream and mediates the effects of the EMT phenomena, a morphological change known to endow cells with capacities of self-renewal and motility. In sum, we linked the CSC concept to the regulation of the Hippo pathway, and provided a mechanistic basis of the control of Hippo kinases by cell polarity (Cordenonsi et al., Cell 2011). Intriguingly, YAP/TAZ regulation by the Hippo pathway control organ growth during development; thus, finding TAZ as determinant of tumor growth supports the hypothesis that tumors are aberrant attempts at de novo organogenesis.

We are now interested in identifying new drugs targeting TAZ and YAP as well as new mediators of their potent biological activity through Hippo dependent and independent pathways.

click here for a list of protocols on detecting YAP and TAZ proteins by western blot, IHC and IF.

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