The Hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications

被引:78
作者
Maugeri-Sacca, Marcello [1 ,2 ]
Barba, Maddalena [1 ,2 ]
Pizzuti, Laura [1 ]
Vici, Patrizia [1 ]
Di Lauro, Luigi [1 ]
Dattilo, Rosanna [3 ]
Vitale, Ilio [2 ]
Bartucci, Monica [4 ]
Mottolese, Marcella [5 ]
De Maria, Ruggero [2 ]
机构
[1] Regina Elena Inst Canc Res, Div Med Oncol B, I-00144 Rome, Italy
[2] Regina Elena Inst Canc Res, Sci Direct, I-00144 Rome, Italy
[3] Ist Super Sanita, Dept Hematol Oncol & Mol Med, I-00161 Rome, Italy
[4] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA
[5] Regina Elena Inst Canc Res, Dept Pathol, I-00144 Rome, Italy
来源
EXPERT REVIEWS IN MOLECULAR MEDICINE | 2015年 / 17卷
关键词
YES-ASSOCIATED PROTEIN; EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELL PROPERTIES; TUMOR-SUPPRESSOR; TRANSCRIPTIONAL COACTIVATOR; PROSPECTIVE IDENTIFICATION; MOLECULAR PORTRAITS; PROMOTES APOPTOSIS; SIGNALING PATHWAY; TEAD/TEF FAMILY;
D O I
10.1017/erm.2015.12
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
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.
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页数:10
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共 108 条
  • [1] Prospective identification of tumorigenic breast cancer cells
    Al-Hajj, M
    Wicha, MS
    Benito-Hernandez, A
    Morrison, SJ
    Clarke, MF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) : 3983 - 3988
  • [2] Genetic variegation of clonal architecture and propagating cells in leukaemia
    Anderson, Kristina
    Lutz, Christoph
    van Delft, Frederik W.
    Bateman, Caroline M.
    Guo, Yanping
    Colman, Susan M.
    Kempski, Helena
    Moorman, Anthony V.
    Titley, Ian
    Swansbury, John
    Kearney, Lyndal
    Enver, Tariq
    Greaves, Mel
    [J]. NATURE, 2011, 469 (7330) : 356 - +
  • [3] [Anonymous], 2014, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Breast Cancer
  • [4] YAP/TAZ Incorporation in the β-Catenin Destruction Complex Orchestrates the Wnt Response
    Azzolin, Luca
    Panciera, Tito
    Soligo, Sandra
    Enzo, Elena
    Bicciato, Silvio
    Dupont, Sirio
    Bresolin, Silvia
    Frasson, Chiara
    Basso, Giuseppe
    Guzzardo, Vincenza
    Fassina, Ambrogio
    Cordenonsi, Michelangelo
    Piccolo, Stefano
    [J]. CELL, 2014, 158 (01) : 157 - 170
  • [5] A cell-based assay to screen stimulators of the Hippo pathway reveals the inhibitory effect of dobutamine on the YAP-dependent gene transcription
    Bao, Yijun
    Nakagawa, Kentaro
    Yang, Zeyu
    Ikeda, Mitsunobu
    Withanage, Kanchanamala
    Ishigami-Yuasa, Mari
    Okuno, Yukiko
    Hata, Shoji
    Nishina, Hiroshi
    Hata, Yutaka
    [J]. JOURNAL OF BIOCHEMISTRY, 2011, 150 (02) : 199 - 208
  • [6] TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells
    Bartucci, M.
    Dattilo, R.
    Moriconi, C.
    Pagliuca, A.
    Mottolese, M.
    Federici, G.
    Di Benedetto, A.
    Todaro, M.
    Stassi, G.
    Sperati, F.
    Amabile, M. I.
    Pilozzi, E.
    Patrizii, M.
    Biffoni, M.
    Maugeri-Sacca, M.
    Piccolo, S.
    De Maria, R.
    [J]. ONCOGENE, 2015, 34 (06) : 681 - 690
  • [7] Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial
    Baselga, Jose
    Bradbury, Ian
    Eidtmann, Holger
    Di Cosimo, Serena
    de Azambuja, Evandro
    Aura, Claudia
    Gomez, Henry
    Dinh, Phuong
    Fauria, Karine
    Van Dooren, Veerle
    Aktan, Gursel
    Goldhirsch, Aron
    Chang, Tsai-Wang
    Horvath, Zsolt
    Coccia-Portugal, Maria
    Domont, Julien
    Tseng, Ling-Min
    Kunz, Georg
    Sohn, Joo Hyuk
    Semiglazov, Vladimir
    Lerzo, Guillermo
    Palacova, Marketa
    Probachai, Volodymyr
    Pusztai, Lajos
    Untch, Michael
    Gelber, Richard D.
    Piccart-Gebhart, Martine
    [J]. LANCET, 2012, 379 (9816) : 633 - 640
  • [8] Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis
    Basu, S
    Totty, NF
    Irwin, MS
    Sudol, M
    Downward, J
    [J]. MOLECULAR CELL, 2003, 11 (01) : 11 - 23
  • [9] Hypoxia inducible factor-1 is activated by transcriptional co-activator with PDZ-binding motif (TAZ) versus WWdomain-containing oxidoreductase (WWOX) in hypoxic microenvironment of bone metastasis from breast cancer
    Bendinelli, Paola
    Maroni, Paola
    Matteucci, Emanuela
    Luzzati, Alessandro
    Perrucchini, Giuseppe
    Desiderio, Maria Alfonsina
    [J]. EUROPEAN JOURNAL OF CANCER, 2013, 49 (11) : 2608 - 2618
  • [10] Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
    Bonnet, D
    Dick, JE
    [J]. NATURE MEDICINE, 1997, 3 (07) : 730 - 737