TY - JOUR
T1 - The Hippo transducers TAZ and YAP in breast cancer: Oncogenic activities and clinical implications
AU - Maugeri-Saccà, Marcello
AU - Barba, Maddalena
AU - Pizzuti, Laura
AU - Vici, Patrizia
AU - Di Lauro, Luigi
AU - Dattilo, Rosanna
AU - Vitale, Ilio
AU - Bartucci, Monica
AU - Mottolese, Marcella
AU - De Maria Marchiano, Ruggero
PY - 2015
Y1 - 2015
N2 - The Hippo signalling is emerging as a tumour suppressor pathway whose function is regulated by an intricate network of intracellular and extracellular cues. Defects in the signal cascade lead to the activation of the Hippo transducers TAZ and YAP. Compelling preclinical evidence showed that TAZ/YAP are often aberrantly engaged in breast cancer (BC), where their hyperactivation culminates into a variety of tumour-promoting functions such as epithelial-to-mesenchymal transition, cancer stem cell generation and therapeutic resistance. Having acquired a more thorough understanding in the biology of TAZ/YAP, and the molecular outputs they elicit, has prompted a first wave of exploratory, clinically-focused analyses aimed at providing initial hints on the prognostic/predictive significance of their expression. In this review, we discuss oncogenic activities linked with TAZ/YAP in BC, and we propose clinical strategies for investigating their role as biomarkers in the clinical setting. Finally, we address the therapeutic potential of TAZ/YAP targeting and the modalities that, in our opinion, should be pursued in order to further study the biological and clinical consequences of their inhibition.
AB - The Hippo signalling is emerging as a tumour suppressor pathway whose function is regulated by an intricate network of intracellular and extracellular cues. Defects in the signal cascade lead to the activation of the Hippo transducers TAZ and YAP. Compelling preclinical evidence showed that TAZ/YAP are often aberrantly engaged in breast cancer (BC), where their hyperactivation culminates into a variety of tumour-promoting functions such as epithelial-to-mesenchymal transition, cancer stem cell generation and therapeutic resistance. Having acquired a more thorough understanding in the biology of TAZ/YAP, and the molecular outputs they elicit, has prompted a first wave of exploratory, clinically-focused analyses aimed at providing initial hints on the prognostic/predictive significance of their expression. In this review, we discuss oncogenic activities linked with TAZ/YAP in BC, and we propose clinical strategies for investigating their role as biomarkers in the clinical setting. Finally, we address the therapeutic potential of TAZ/YAP targeting and the modalities that, in our opinion, should be pursued in order to further study the biological and clinical consequences of their inhibition.
KW - Adaptor Proteins, Signal Transducing
KW - Antineoplastic Agents
KW - Breast Neoplasms
KW - Clinical Trials as Topic
KW - Drug Resistance, Neoplasm
KW - Epithelial-Mesenchymal Transition
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors
KW - Intracellular Signaling Peptides and Proteins
KW - Molecular Biology
KW - Molecular Medicine
KW - Neoplastic Stem Cells
KW - Phosphoproteins
KW - Phosphorylation
KW - Signal Transduction
KW - Adaptor Proteins, Signal Transducing
KW - Antineoplastic Agents
KW - Breast Neoplasms
KW - Clinical Trials as Topic
KW - Drug Resistance, Neoplasm
KW - Epithelial-Mesenchymal Transition
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors
KW - Intracellular Signaling Peptides and Proteins
KW - Molecular Biology
KW - Molecular Medicine
KW - Neoplastic Stem Cells
KW - Phosphoproteins
KW - Phosphorylation
KW - Signal Transduction
UR - http://hdl.handle.net/10807/112038
UR - http://journals.cambridge.org
U2 - 10.1017/erm.2015.12
DO - 10.1017/erm.2015.12
M3 - Article
SN - 1462-3994
VL - 17
SP - N/A-N/A
JO - Expert Reviews in Molecular Medicine
JF - Expert Reviews in Molecular Medicine
ER -