Transcriptional Coactivator with PDZ-binding Motif Is Essential for Normal Alveolarization in Mice

Mitani, Akihisa; Nagase, Takahide; Fukuchi, Kazunori; Aburatani, Hiroyuki; Makita, Ryosuke; Kurihara, Hiroki

doi:10.1164/rccm.200812-1827oc

Cited by 94 publications

(87 citation statements)

References 46 publications

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“…In addition to the kidney defects discussed above, Taz knockout mice were observed to display alveolarization defects that resemble those seen in human emphysema (Hossain et al, 2007;Makita et al, 2008;Mitani et al, 2009;Tian et al, 2007). TAZ associates with and promotes the activity of TTF1 (NKX2.1), a transcription factor essential for specifying the lung (Park et al, 2004).…”

Section: Lungmentioning

confidence: 96%

“…The first evidence for the importance of Hippo signaling in kidney development emerged from analyses of Taz knockout mice, which develop polycystic kidneys (Hossain et al, 2007;Makita et al, 2008;Mitani et al, 2009;Tian et al, 2007). The large cysts found in Taz knockout kidneys exhibit elevated levels of PC2, a calcium-permeable cation channel that has roles in ciliogenesis and is commonly dysregulated in polycystic kidney disease (Tian et al, 2007).…”

Section: Kidneymentioning

confidence: 99%

“…However, whether this relationship is important for the roles of TAZ in lung development is unclear, as Taz knockout lungs do not exhibit any changes in TTF1 target gene expression. Intriguingly, heterozygous deletion of Taz was found to confer resistance to bleomycin-induced lung fibrosis (Mitani et al, 2009), suggesting that TAZ might be a key factor promoting fibrotic responses. Conditional knockout of Mst1/2 in the respiratory epithelium also leads to lethal respiratory failure , but these defects were not attributed to changes in TAZ or YAP localization.…”

Section: Lungmentioning

confidence: 99%

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The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease

2014

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Studies over the past 20 years have defined the Hippo signaling pathway as a major regulator of tissue growth and organ size. Diverse roles for the Hippo pathway have emerged, the majority of which in vertebrates are determined by the transcriptional regulators TAZ and YAP (TAZ/YAP). Key processes regulated by TAZ/YAP include the control of cell proliferation, apoptosis, movement and fate. Accurate control of the levels and localization of these factors is thus essential for early developmental events, as well as for tissue homeostasis, repair and regeneration. Recent studies have revealed that TAZ/YAP activity is regulated by mechanical and cytoskeletal cues as well as by various extracellular factors. Here, I provide an overview of these and other regulatory mechanisms and outline important developmental processes controlled by TAZ and YAP.

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Section: Lungmentioning

confidence: 96%

Section: Kidneymentioning

confidence: 99%

Section: Lungmentioning

confidence: 99%

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The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease

2014

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“…TAZ has also been shown to regulate stem cell differentiation and renewal through modulation of the transcription factors PPARg, Runx2 and Smad (Hong et al, 2005;Varelas et al, 2008). Moreover, TAZ knockout mice develop polycystic kidney disease and emphysema (Mitani et al, 2009;Tian et al, 2007). Recently, TAZ has been identified as a component of an emerging Hippo-LATS tumor suppressor pathway that has important roles in regulating cell proliferation, apoptosis, tumor formation and organ size in both Drosophila and mammals (Harvey and Tapon, 2007;Saucedo and Edgar, 2007;Zhao et al, 2007Zhao et al, , 2008Zeng and Hong, 2008;Hergovich and Hemmings, 2009;Wang et al, 2009;Visser and Yang, 2010).…”

Section: Introductionmentioning

confidence: 99%

TAZ is a novel oncogene in non-small cell lung cancer

et al. 2011

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Transcriptional coactivator with PDZ-binding motif (TAZ) is a transcriptional coactivator involved in the differentiation of stem cell as well as the development of multiple organs. Recently, TAZ has also been identified as a major component of the novel Hippo-LATS tumor suppressor pathway and to function as an oncogene in breast cancer. We show for the first time that TAZ is an oncogene in non-small cell lung cancer (NSCLC). Our results show that TAZ is overexpressed in NSCLC cells and that lentivirus-mediated overexpression of TAZ in HBE135 immortalized human bronchial epithelial cells causes increased cell proliferation and transformation, which can be restored back to its original levels by knockdown of TAZ. In addition, short-hairpin RNA (shRNA)-mediated knockdown of TAZ expression in NSCLC cells suppresses their proliferation and anchorage-independent growth in vitro, and tumor growth in mice in vivo, which can be reversed by re-introduction of shRNA-resistant TAZ into TAZ-knockdown NSCLC cells. These results indicate that TAZ is an oncogene and has an important role in tumorigenicity of NSCLC cells. Therefore, TAZ may present a novel target for the future diagnosis, prognosis and therapy of lung cancer.

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“…Instead, connective tissue growth factor (CTGF) was significantly reduced in Taz deficient lungs. The Taz-Nkx2.1-CTGF axis was proposed to be critical for lung alveolarization (18). The lung specific-Taz knockout mice are not been studied.…”

Section: Tazmentioning

confidence: 99%