A Role for TAZ in Migration, Invasion, and Tumorigenesis of Breast Cancer Cells

Chan, Siew Wee; Lim, Chun Jye; Guo, Ke; Ng, Chee Peng; Lee, Ian; Hunziker, Walter; Zeng, Qi; Hong, Wanjin

doi:10.1158/0008-5472.can-07-2696

Cited by 437 publications

(501 citation statements)

References 22 publications

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“…34 Hence, it would appear that TAZ is a potent activator of cell transformation and tumorigenesis. 35,36 On the basis of this evidence, and given the importance of epithelial to mesenchymal transition and stemness in the carcinogenesis of certain subtypes of endometrial tumors, 3,4 we analyzed TAZ expression in a series of 143 endometrial carcinoma samples. We found that TAZ expression was associated with high-grade endometrial tumors, mainly represented by undifferentiated endometrial carcinomas and endometrial carcinosarcomas.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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. Modern Pathology (2015Pathology ( ) 28, 1492Pathology ( -1503 doi:10.1038/modpathol.2015 published online 18 September 2015 In developed countries, endometrial carcinoma is the most common malignant tumor of the female genital tract. 1 On the basis of epidemiological, clinical, pathological, and molecular features, endometrial carcinoma can be classified into at least two main categories: 2 type I estrogen-dependent carcinomas that account for 80-85% of cases and that are typically represented by low-grade (grade 1 and 2) endometrioid carcinomas, and type II endometrial carcinomas that are not estrogen dependent and that are mainly represented by a serous subtype but also by other high-grade histological tumors like clear cell or undifferentiated carcinomas. 2 In endometrial carcinoma, the epithelial to mesenchymal transition has been associated with high-grade and aggressive features. [3][4][5][6] Epithelial to

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Furthermore, genomic amplification and elevated expression and nuclear localization of YAP has been observed in human cancers (Overholtzer et al, 2006;Zender et al, 2006;Dong et al, 2007;Zhao et al, 2007;Steinhardt et al, 2008;Hall et al, 2010). Overexpression of TAZ has also been noted in human breast cancer samples and non-small cell lung cancer cell lines (Chan et al, 2008;Zhou et al, 2011b). Similar to YAP overexpression, ablation of the Hippo pathway components Mer and Sav and double knockout of Mst1/2 in mice result in liver enlargement and tumor formation characteristic of HCC and cholangiocarcinoma (CC) (Zhou et al, 2009;Benhamouche et al, 2010;Lee et al, 2010;Lu et al, 2010;Song et al, 2010;.…”

Section: The Mammalian Hippo Pathwaymentioning

confidence: 99%

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

et al. 2012

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This pathway was first found to inhibit cell proliferation and promote apoptosis, therefore regulating cell number and organ size in both Drosophila and mammals. However, in several organs, disturbance of the pathway leads to specific expansion of the progenitor cell compartment and manipulation of the pathway in embryonic stem cells strongly affects their self-renewal and differentiation. In this review, we summarize current observations on roles of the Hippo pathway in different types of stem cells and discuss how these findings changed our view on the Hippo pathway in organ development and tumorigenesis.

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“…Of particular interest to this study is the mammary gland. Although several studies have implicated dysregulation of the Hippo pathway in breast cancers (Overholtzer et al 2006;Chan et al 2008;Lei et al 2008;Cordenonsi et al 2011), its physiological role in mammary gland development is unknown. Even in breast tumorigenesis, the contribution of Hippo signaling is controversial.…”

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confidence: 99%

A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis

et al. 2014

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Despite recent progress, the physiological role of Hippo signaling in mammary gland development and tumorigenesis remains poorly understood. Here we show that the Hippo pathway is functionally dispensable in virgin mammary glands but specifically required during pregnancy. In contrast to many other tissues, hyperactivation of YAP in mammary epithelia does not induce hyperplasia but leads to defects in terminal differentiation. Interestingly, loss of YAP causes no obvious defects in virgin mammary glands but potently suppresses oncogeneinduced mammary tumors. The selective requirement for YAP in oncogenic growth highlights the potential of YAP inhibitors as molecular targeted therapies against breast cancers.

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A Role for TAZ in Migration, Invasion, and Tumorigenesis of Breast Cancer Cells

Cited by 437 publications

References 22 publications

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

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

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis

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