title: The Hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications.
abstract: 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.
authors.affiliation: Division of Medical Oncology B,Regina Elena National Cancer Institute,Rome,Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.affiliation: Division of Medical Oncology B,Regina Elena National Cancer Institute,Rome,Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
authors.affiliation: Division of Medical Oncology B,Regina Elena National Cancer Institute,Rome,Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pizzuti
authors.affiliation: Division of Medical Oncology B,Regina Elena National Cancer Institute,Rome,Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.affiliation: Division of Medical Oncology B,Regina Elena National Cancer Institute,Rome,Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Lauro
authors.affiliation: Department of Hematology,Oncology and Molecular Medicine,Istituto Superiore di Sanità,Rome,Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Dattilo
authors.affiliation: Scientific Direction,Regina Elena National Cancer Institute,Rome,Italy.
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.affiliation: Rutgers Cancer Institute of New Jersey,New Brunswick,New Jersey,USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Bartucci
authors.affiliation: Department of Pathology,Regina Elena National Cancer Institute,Rome,Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.affiliation: Scientific Direction,Regina Elena National Cancer Institute,Rome,Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human