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

Varelas, Xaralabos

doi:10.1242/dev.102376

Cited by 555 publications

(527 citation statements)

References 156 publications

(212 reference statements)

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“…Elevated levels of TGF-b are associated with both fibrosis and cardiac hypertrophy (33,34). We evaluated signaling through canonical and noncanonical mediators of fibrosis and hypertrophy in response to TGF-b, including ERK, GSK-3b/ b-catenin (35), pSMAD2/SMAD2 (36), Akt (37), and YAP (38). Although we did not observe any robust changes in these effectors, these pathways are known to be activated in the short term in response to pressure overload and remain only moderately elevated at later time points (34,39).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat–Fed Diabetic Mice

et al. 2015

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Dipeptidyl peptidase-4 (DPP4) inhibitors used for the treatment of type 2 diabetes are cardioprotective in preclinical studies; however, some cardiovascular outcome studies revealed increased hospitalization rates for heart failure (HF) among a subset of DPP4 inhibitor–treated subjects with diabetes. We evaluated cardiovascular function in young euglycemic Dpp4−/− mice and in older, high fat–fed, diabetic C57BL/6J mice treated with either the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide or the highly selective DPP4 inhibitor MK-0626. We assessed glucose metabolism, ventricular function and remodeling, and cardiac gene expression profiles linked to inflammation and fibrosis after transverse aortic constriction (TAC) surgery, a pressure-volume overload model of HF. Young euglycemic Dpp4−/− mice exhibited a cardioprotective response after TAC surgery or doxorubicin administration, with reduced fibrosis; however, cardiac mRNA analysis revealed increased expression of inflammation-related transcripts. Older, diabetic, high fat–fed mice treated with the GLP-1R agonist liraglutide exhibited preservation of cardiac function. In contrast, diabetic mice treated with MK-0626 exhibited modest cardiac hypertrophy, impairment of cardiac function, and dysregulated expression of genes and proteins controlling inflammation and cardiac fibrosis. These findings provide a model for the analysis of mechanisms linking fibrosis, inflammation, and impaired ventricular function to DPP4 inhibition in preclinical studies.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat–Fed Diabetic Mice

et al. 2015

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“…Furthermore, the findings augment an emerging body of literature on the role of YAP in cancer progression, with important implications for understanding the function of YAP in cell survival and growth. 8,9 Dual basic and translational investigations promise to shed light on the emerging role of YAP in cancer biology and therapy.…”

Section: Discussionmentioning

confidence: 99%

The Hippo effector YAP regulates the response of cancer cells to MAPK pathway inhibitors

Bivona

2015

Molecular & Cellular Oncology

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“…Yki activation leads to increased cell proliferation in a variety of tissues (79). To test whether the rate of cell division is accelerated by lkb1 loss in the larval CNS, we analyzed PH3 staining in the third instar larval VNC.…”

Section: Significancementioning

confidence: 99%

Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system

Gailite

Aerne

Tapon

2015

Proc. Natl. Acad. Sci. U.S.A.

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The Hippo (Hpo) pathway is a highly conserved tumor suppressor network that restricts developmental tissue growth and regulates stem cell proliferation and differentiation. At the heart of the Hpo pathway is the progrowth transcriptional coactivator Yorkie [Yki–Yes-activated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) in mammals]. Yki activity is restricted through phosphorylation by the Hpo/Warts core kinase cascade, but increasing evidence indicates that core kinase-independent modes of regulation also play an important role. Here, we examine Yki regulation in the Drosophila larval central nervous system and uncover a Hpo/Warts-independent function for the tumor suppressor kinase liver kinase B1 (LKB1) and its downstream effector, the energy sensor AMP-activated protein kinase (AMPK), in repressing Yki activity in the central brain/ventral nerve cord. Although the Hpo/Warts core cascade restrains Yki in the optic lobe, it is dispensable for Yki target gene repression in the late larval central brain/ventral nerve cord. Thus, we demonstrate a dramatically different wiring of Hpo signaling in neighboring cell populations of distinct developmental origins in the central nervous system.

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

Cited by 555 publications

References 156 publications

Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat–Fed Diabetic Mice

Inhibition of Dipeptidyl Peptidase-4 Impairs Ventricular Function and Promotes Cardiac Fibrosis in High Fat–Fed Diabetic Mice

The Hippo effector YAP regulates the response of cancer cells to MAPK pathway inhibitors

Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system

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