title: A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer.
abstract: Although TAZ, the final effector of the Hippo pathway that modulates epithelial to mesenchymal transition and stemness, has been implicated in the development of different types of cancer, its role in endometrial cancer has not yet been studied. Thus, we evaluated the expression of TAZ in different types of endometrial cancer by immunohistochemistry. TAZ expression was detected in 76% of undifferentiated endometrial carcinomas, 54% of endometrial carcinosarcomas, 46% of endometrial serous carcinomas, 36% of grade 3 endometrioid carcinomas, and 18% of grade 1-2 endometrioid carcinomas, with statistically significant differences. We analyzed the WWTR1 gene that encodes TAZ by FISH and MassARRAY spectrometry, ruling out gene amplification and differential promoter methylation as the main mechanisms that modulate TAZ expression in endometrial tumors. However, we did detect a significant association between Scribble hypoexpression and delocalization with TAZ expression. Moreover, we demonstrated that TAZ promoted invasiveness, and it favored cell motility and tumor growth, in endometrial cancer cell lines. In addition, TAZ expression was associated with the transition from an epithelial to mesenchymal phenotype, both in vitro and in human tumors. Together, these data reveal a previously unknown role for TAZ and the Hippo pathway in the progression of aggressive subtypes of endometrial cancer.
authors.affiliation: Department of Pathology, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Romero-Pérez
authors.affiliation: Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.|Translational Research Laboratory, MD Anderson International Foundation, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Sanz
authors.affiliation: Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.|Translational Research Laboratory, MD Anderson International Foundation, Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Mota
authors.affiliation: Department of Pathology, Hospital Universitario Ramón y Cajal, Instituto de Investigación Sanitaria Ramón y Cajal (IRYCIS), Universidad de Alcalá, Madrid, Spain.
authors.forename: Susanna
authors.initials: S
authors.lastname: Leskelä
authors.affiliation: Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Hergueta-Redondo
authors.affiliation: Department of Pathology, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Díaz-Martín
authors.affiliation: Department of Pathology, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: M Angeles
authors.initials: MA
authors.lastname: López-García
authors.affiliation: Department of Pathology, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Castilla
authors.affiliation: Department of Molecular Cytogenetics, MD Anderson Cancer Center, Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Martínez-Ramírez
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Center, Memorial Hospital, New York, NY, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.affiliation: Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, Lleida, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.affiliation: Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.|Translational Research Laboratory, MD Anderson International Foundation, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Moreno-Bueno
authors.affiliation: Department of Pathology, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.|Department of Pathology, Hospital Universitario Ramón y Cajal, Instituto de Investigación Sanitaria Ramón y Cajal (IRYCIS), Universidad de Alcalá, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Palacios
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D064593:Heterografts; D000090683:Hippo Signaling Pathway; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D017346:Protein Serine-Threonine Kinases