A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

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.
This work was supported by grants from Spanish Ministry of Health, Instituto de Salud Carlos III (RD12/0036/0064 and PI13/02477 to JP and RETICC RD12/0036/0007 and PI13/00132 to GM-B); the European Development Regional Fund, ‘A way to achieve Europe’ EDRF to JP; the Community of Madrid (S2010/BMD-2303) and AECC Foundation to GMB; and by TV3 La Marató-2013 to GM-B and JP. LR-P is a recipient of a PFIS fellowship (Grant No. F109/00193). PG-S is funded by the AECC-2011. AM is a predoctoral student supported by a FPU fellowship (Spanish Ministry of Education, Culture and Sport). JD-M is a PhD researcher funded by the Consejería de Salud, Junta de Andalucía (PI0581/2009). MH-R is a PhD researcher funded by Community of Madrid. MAC is a PhD researcher funded by the ISCIII (RD06/0020/0013).