Published: 2016-02-16

TAZ oncogene as a prognostic factor in breast cancer

Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poland
Department of Cancer Immunology, Poznan University of Medical Sciences, Poland
breast cancer prognosis cancer stem cells Hippo pathway targeted therapy


Breast cancer is the most frequently diagnosed cancer in females and one of the main causes of cancer related deaths. Breast cancer in the metastatic stage is related with poor prognosis. Metastasis is the process whereby cancer cells travel to and colonize distant sites through the lymphatic system or bloodstream, which usually indicates a poor prognosis. The metastatic cascade involves several molecular and cellular interactions and different signaling pathaways. Recently the Hippo signaling has emerged as an important regulatory pathway in cancer. The Hippo target protein TAZ has been reported as a novel oncogene that may have important role in the development of breast cancer. Its overexpression promotes cancer stem cell formation and epithelial–mesenchymal transition in many human cancers. In breast TAZ seems to play a critical developmental role and in breast cancer is one of the factors involved in therapeutic resistance and clinical relapse. Herein, we review the biological functions of TAZ and summarize the current knowledge and opportunities for therapeutic intervention in this field.


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  1. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, JK Willson V, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science. Oct. 2006;314(5797):268–274.
  2. Lei Q-Y, Zhang H, Zhao B, Z-Y Zha, Bai F, X-H Pei, Zhao S, Xiong Y, K-L Guan. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. Mol Cell Biol. Apr. 2008;28(7):2426–2436.
  3. Hao Y, Chun A, Cheung K, Rashidi B, Yang X. Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem. Feb. 2008;283(9):5496–5509.
  4. Sudol M, Sliwa K, Russo T. Functions of WW domains in the nucleus. FEBS Lett. Feb. 2001;490(3):190–195.
  5. Chan SW, Lim CJ, Guo K, Ng CP, Lee I, Hunziker W, Zeng Q, Hong W. A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells. Cancer Res. Apr. 2008;68(8):2592–2598.
  6. Skibinski A, Breindel JL, Prat A, Galván P, Smith E, Rolfs A, Gupta PB, LaBaer J, Kuperwasser C. The Hippo Transducer TAZ Interacts with the SWI/SNF Complex to Regulate Breast Epithelial Lineage Commitment. Cell Rep. Mar. 2014;6(6):1059–1072.
  7. Shi P, Feng J, Chen C. Hippo pathway in mammary gland development and breast cancer. Acta Biochim. Biophys. Sin. Jan. 2015;47(1):53–59.
  8. Zhao B, Li L, Lei Q, K-L Guan. The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev. May 2010;24(9):862–874.
  9. Avruch J, Zhou D, Bardeesy N. YAP oncogene overexpression supercharges colon cancer proliferation. Cell Cycle Georget Tex. Mar. 2012;11(6):1090–1096.
  10. de Cristofaro T, Di Palma T, Ferraro A, Corrado A, Lucci V, Franco R, Fusco A, Zannini M. TAZ/WWTR1 is overexpressed in papillary thyroid carcinoma. Eur J Cancer Oxf Engl. 1990. Apr. 2011;47(6):926–933.
  11. Yuen H-F, CM McCrudden, Y-H Huang, Tham JM, Zhang X, Zeng Q, S-D Zhang, Hong W. TAZ Expression as a Prognostic Indicator in Colorectal Cancer. PLoS ONE. Jan. 2013;8(1):e54211.
  12. Wang Y, Dong Q, Zhang Q, Li Z, Wang E, Qiu X. Overexpression of yes-associated protein contributes to progression and poor prognosis of non-small-cell lung cancer. Cancer Sci. May 2010;101(5):1279–1285.
  13. Xu MZ, Yao T-J, NP Lee Y, IO Ng L, Chan Y-T, Zender L, Lowe SW, RT Poon P, Luk JM. Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer. Oct. 2009;115(19):4576–4585.
  14. Xie M, Zhang L, He C-S, Hou J-H, Lin S-X, Hu Z-H, Xu F, Zhao H-Y. Prognostic significance of TAZ expression in resected non-small cell lung cancer. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. May 2012;7(5):799–807.
  15. Yue G, Sun X, Gimenez-Capitan A, Shen J, Yu L, Teixido C, Guan W, Rosell R, Liu B, Wei J. TAZ Is Highly Expressed in Gastric Signet Ring Cell Carcinoma. BioMed Res Int. 2014;1–6.
  16. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. Jan. 2010;140(1):62–73.
  17. Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, Daidone MG, Dupont S, Basso G, Bicciato S, Piccolo S. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell. Nov. 2011;147(4):759–772.
  18. Bartucci M, Dattilo R, Moriconi C, Pagliuca A, Mottolese M, Federici G, Benedetto AD, Todaro M, Stassi G, Sperati F, Amabile MI, Pilozzi E, Patrizii M, Biffoni M, M Maugeri-Sacca, Piccolo S, De Maria R. TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells. Oncogene. Feb. 2015;34(6):681–690.
  19. Guo L, Teng L. YAP/TAZ for cancer therapy: Opportunities and challenges (Review). Int J Oncol Apr. 2015;46(4):1444–1452.
  20. Li Y-W, Shen H, Frangou C, Yang N, Guo J, Xu B, Bshara W, Shepherd L, Zhu Q, Wang J, Hu Q, Liu S, Morrison CD, Sun P, Zhang J. Characterization of TAZ domains important for the induction of breast cancer stem cell properties and tumorigenesis. Cell Cycle Georget Tex. 2015;14(1):146–156.
  21. Zhang H, Liu C-Y, Zha Z-Y, Zhao B, Yao J, Zhao S, Xiong Y, Lei Q-Y, Guan K-L. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J Biol Chem. May 2009;284(20):13355–13362.
  22. Zhao D, Zhi X, Zhou Z, Chen C. TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis. Carcinogenesis. Jan. 2012;33(1):59–67.
  23. Al-Hajj M, Wicha MS, A Benito-Hernandez, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci. Apr. 2003;100(7):3983–3988.
  24. Frangou C, Li Y-W, Shen H, Yang N, Wilson KE, Blijlevens M, Guo J, Nowak NJ, Zhang J. Molecular profiling and computational network analysis of TAZ-mediated mammary tumorigenesis identifies actionable therapeutic targets. Oncotarget. Dec. 2014;5(23):12166–12176.
  25. Lai D, S Visser-Grieve, Yang X. Tumour suppressor genes in chemotherapeutic drug response. Biosci Rep. Aug. 2012;32(4):361–374.
  26. Lai D, Ho KC, Hao Y, Yang X. Taxol resistance in breast cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF. Cancer Res. Apr. 2011;71(7):2728–2738.
  27. Vici P, Mottolese M, Pizzuti L, Barba M, Sperati F, Terrenato I, Di Benedetto A, Natoli C, Gamucci T, Angelucci D, Ramieri MT, Di Lauro L, Sergi D, Bartucci M, Dattilo R, Pagliuca A, De Maria R, M Maugeri-Sacca. The Hippo transducer TAZ as a biomarker of pathological complete response in HER2-positive breast cancer patients treated with trastuzumab-based neoadjuvant therapy. Oncotarget. Oct. 2014;5(20):9619–9625.
  28. Stanger BZ. Quit your YAPing: a new target for cancer therapy. Genes Dev. Jun. 2012;26(12):1263–1267.
  29. Liu-Chittenden Y, Huang B, Shim JS, Chen Q, Lee S-J, Anders RA, Liu JO, Pan D. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. Jun. 2012;26(12):1300–1305.
  30. Anand R, Maksimoska J, Pagano N, Wong EY, Gimotty PA, Diamond SL, Meggers E, Marmorstein R. Toward the development of a potent and selective organoruthenium mammalian sterile 20 kinase inhibitor. J Med Chem. Mar. 2009;52(6):1602–1611.
  31. Santucci M, Vignudelli T, Ferrari S, Mor M, Scalvini L, Bolognesi ML, Uliassi E, Costi MP. The Hippo Pathway and YAP/TAZ–TEAD Protein–Protein Interaction as Targets for Regenerative Medicine and Cancer Treatment: Miniperspective. J Med Chem Mar. 2015: p. 150311145040001.
  32. Sansores-Garcia L, Bossuyt W, Wada K-I, Yonemura S, Tao C, Sasaki H, Halder G. Modulating F-actin organization induces organ growth by affecting the Hippo pathway. EMBO J. Jun. 2011;30(12):2325–2335.
  33. Fernández BG, Gaspar P, C Brás-Pereira, Jezowska B, Rebelo SR, Janody F. Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila. Dev. Camb. Engl. Jun. 2011;138(11): 2337–2346.
  34. Yu F-X, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H, Fu X-D, Mills GB, Guan K-L. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. Aug. 2012;150(4): 780–791.
  35. Miller E, Yang J, DeRan M, Wu C, Su AI, GM Bonamy C, Liu J, Peters EC, Wu X. Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAP. Chem Biol. Aug. 2012;19(8):955–962.
  36. Fleming JK, Wojciak JM, Campbell M-A, Huxford T. Biochemical and structural characterization of lysophosphatidic Acid binding by a humanized monoclonal antibody. J Mol Biol. May 2011;408(3):462–476.
  37. Ponnusamy S, Selvam SP, Mehrotra S, Kawamori T, Snider AJ, Obeid LM, Shao Y, Sabbadini R, Ogretmen B. Communication between host organism and cancer cells is transduced by systemic sphingosine kinase 1/sphingosine 1-phosphate signalling to regulate tumour metastasis. EMBO Mol Med. Aug. 2012;4(8):761–775.
  38. Wootten D, Christopoulos A, Sexton PM. Emerging paradigms in GPCR allostery: implications for drug discovery. Nat Rev Drug Discov. Aug. 2013;12(8):630–644.
  39. Azzolin L, Zanconato F, Bresolin S, Forcato M, Basso G, Bicciato S, Cordenonsi M, Piccolo S. Role of TAZ as mediator of Wnt signaling. Cell. Dec. 2012;151(7):1443–1456.
  40. Sorrentino G, Ruggeri N, Specchia V, Cordenonsi M, Mano M, Dupont S, Manfrin A, Ingallina E, Sommaggio R, Piazza S, Rosato A, Piccolo S, Del Sal G. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat. Cell Biol. Mar. 2014;16(4):357–366.
  41. Mi W, Lin Q, Childress C, Sudol M, Robishaw J, Berlot CH, Shabahang M, Yang W. Geranylgeranylation signals to the Hippo pathway for breast cancer cell proliferation and migration. Oncogene. Aug. 2014.
  42. Habbig S, Bartram MP, Müller RU, Schwarz R, Andriopoulos N, Chen S, Sägmüller JG, Hoehne M, Burst V, Liebau MC, Reinhardt HC, Benzing T, Schermer B. NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. J Cell Biol. May 2011;193(4):633–642.
  43. Habbig S, Bartram MP, Sägmüller JG, Griessmann A, Franke M, Müller R-U, Schwarz R, Hoehne M, Bergmann C, Tessmer C, Reinhardt HC, Burst V, Benzing T, Schermer B. The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ. Hum Mol Genet. Dec. 2012;21(26):5528–5538.
  44. Chen Q, Zhang N, Gray RS, Li H, Ewald AJ, Zahnow CA, Pan D. A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis. Genes Dev. Mar. 2014;28(5):432–437.

How to Cite

Glapa A, Nijak A. TAZ oncogene as a prognostic factor in breast cancer. JMS [Internet]. 2016Feb.16 [cited 2020Aug.5];84(2):107-12. Available from: