title: The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells.
abstract: 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.
authors.affiliation: Department of Histology, Microbiology, and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy. michelangelo.cordenonsi@unipd.it
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Cordenonsi
authors.forename: Francesca
authors.initials: F
authors.lastname: Zanconato
authors.forename: Luca
authors.initials: L
authors.lastname: Azzolin
authors.forename: Mattia
authors.initials: M
authors.lastname: Forcato
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.forename: Chiara
authors.initials: C
authors.lastname: Frasson
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inui
authors.forename: Marco
authors.initials: M
authors.lastname: Montagner
authors.forename: Anna R
authors.initials: AR
authors.lastname: Parenti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poletti
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Sirio
authors.initials: S
authors.lastname: Dupont
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.forename: Stefano
authors.initials: S
authors.lastname: Piccolo
mesh_terms: D000217:Acyltransferases; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016764:Cell Polarity; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C480591:SCRIB protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000217:Acyltransferases; C108675:TAFAZZIN protein, human