Hippo pathway and breast cancer stem cells

- Cancer stem cell features are maintained by specific pathways and environmental cues.
- Hippo is a tumor suppressor pathway with profound impact on stem cell biology.
- Activation of Hippo transducers is associated with breast cancer stem cells.
- Hippo pathway analysis in breast cancer samples may unveil novel biomarkers.

Tumors contain a specialized subset of cells with unique properties, such as self-renewal and tumorigenic potential. These cancer stem-like cells (CSCs) are supposed to be responsible for therapeutic resistance and metastatic spread. Functional characterization of breast CSCs (BCSCs) is beginning to shed light on molecular networks which are specifically activated in this cellular compartment, and that account for the retention/acquisition of stem-like features. The Hippo tumor suppressor pathway has increasingly been tied to breast cancer. Altered Hippo activity, or Hippo-independent mechanisms, mediate the activation of the Hippo transducers TAZ and YAP. When this occurs, cancer cells acquire more aggressive traits. In the realm of BCSCs, improper TAZ/YAP activity sustains self-renewal, resistance to conventional anticancer agents, and metastatic dissemination. In this review, we highlight the involvement of TAZ and YAP in mammary gland development and in BCSCs. We also discuss potential strategies for transferring this information into the clinical setting.