The Hippo Transducer TAZ Confers Cancer Stem Cell-Related Traits on Breast Cancer Cells

被引：1113

作者：

Cordenonsi, Michelangelo ^{[1
]}

Zanconato, Francesca ^{[1
]}

Azzolin, Luca ^{[1
]}

Forcato, Mattia ^{[2
]}

Rosato, Antonio ^{[3
,4
]}

Frasson, Chiara ^{[5
]}

Inui, Masafumi ^{[1
]}

Montagner, Marco ^{[1
]}

Parenti, Anna R. ^{[6
]}

Poletti, Alessandro ^{[7
]}

Daidone, Maria Grazia ^{[8
]}

Dupont, Sirio ^{[1
]}

Basso, Giuseppe ^{[5
]}

Bicciato, Silvio ^{[2
]}

Piccolo, Stefano ^{[1
]}

机构：

[1] Univ Padua, Sch Med, Dept Histol Microbiol & Med Biotechnol, I-35126 Padua, Italy

[2] Univ Modena & Reggio Emilia, Dept Biomed Sci, Ctr Genome Res, I-41100 Modena, Italy

[3] Univ Padua, Dept Oncol & Surg Sci, I-35126 Padua, Italy

[4] Ist Oncol Veneto IOV, I-35126 Padua, Italy

[5] Univ Padua, Dept Pediat, I-35128 Padua, Italy

[6] Univ Padua, Sect Pathol, Dept Med Diagnost Sci & Special Therapies, I-35126 Padua, Italy

[7] Hosp San Bassiano, Div Anat Pathol, I-36061 Bassano Del Grappa, Italy

[8] Ist Nazl Tumori, Fdn IRCCS, I-20133 Milan, Italy

来源：

CELL | 2011年 / 147卷 / 04期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; GENE-EXPRESSION SIGNATURE; IN-VITRO PROPAGATION; TUMORIGENESIS; POLARITY; METASTASIS; PATHWAY; TUMORS;

D O I：

10.1016/j.cell.2011.09.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：759 / 772

页数：14

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