A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer Journal Article
| Authors: | Romero-Pérez, L.; Garcia-Sanz, P.; Mota, A.; Leskelä, S.; Hergueta-Redondo, M.; Díaz-Martín, J.; López-García, M. A.; Castilla, M. A.; Martínez-Ramírez, A.; Soslow, R. A.; Matias-Guiu, X.; Moreno-Bueno, G.; Palacios, J. |
| Article 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. |
| Keywords: | immunohistochemistry; signal transduction; human tissue; protein expression; unclassified drug; human cell; major clinical study; methylation; cancer growth; endometrioid carcinoma; endometrium carcinoma; endometrium cancer; mass spectrometry; microrna; gene amplification; genetic association; transcription factor; uvomorulin; fluorescence in situ hybridization; messenger rna; nerve cell adhesion molecule; heat shock protein 90; transcription factor slug; cell motility; vimentin; hippo protein; epithelial mesenchymal transition; osteonectin; high mobility group a2 protein; human; female; priority journal; article; transcription factor zeb1; claudin 1; fizzy related protein; taz protein; transcription factor 7 like 1; transcription factor zeb2; endometrium carcinosarcoma; endometrium serous carcinoma |
| Journal Title: | Modern Pathology |
| Volume: | 28 |
| Issue: | 11 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2015-11-01 |
| Start Page: | 1492 |
| End Page: | 1503 |
| Language: | English |
| DOI: | 10.1038/modpathol.2015.102 |
| PROVIDER: | scopus |
| PUBMED: | 26381823 |
| DOI/URL: | |
| Notes: | Export Date: 2 December 2015 -- Source: Scopus |
