The clinically used photosensitizer Verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation

Brodowska, Katarzyna; Al-Moujahed, Ahmad; Marmalidou, Anna; Hörste, Melissa Meyer zu; Cichy, Joanna; Miller, Joan W.; Gragoudas, Evangelos S.; Vavvas, Demetrios G.

doi:10.1016/j.exer.2014.04.011

Cited by 199 publications

(208 citation statements)

References 55 publications

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“…22 We used a pan-TEAD antibody and found that exposure of LLCPK-Cl4 cells to high glucose increased YAP association with TEAD ( Figure 4A). Verteporfin, a well characterized inhibitor of YAP-TEAD interactions, 32,33 significantly inhibited the proliferative effect of high glucose in LLCPK-Cl4 cells ( Figure 4B). …”

Section: Exposure Of Renal Epithelial Cells Tomentioning

confidence: 99%

Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic Kidney

Chen¹,

Harris

2015

JASN

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Activation of the EGF receptor (EGFR) or the Hippo signaling pathway can control cell proliferation, apoptosis, and differentiation, and the dysregulation of these pathways can contribute to tumorigenesis. Previous studies showed that activation of EGFR signaling in renal epithelial cells can exacerbate diabetic kidney injury. Moreover, EGFR has been implicated in regulating the Hippo signaling pathway in Drosophila; thus, we examined this potential interaction in mammalian diabetic kidney disease. Yes-associated protein (YAP) is a transcriptional regulator regulated by the Hippo signaling pathway. We found YAP protein expression and phosphorylation were upregulated in diabetic mouse renal proximal tubule epithelial cells, which were inhibited in diabetic proximal tubule EGFR-knockout mice (EGFR ptKO ) or administration of an EGFR tyrosine kinase inhibitor erlotinib. Furthermore, activation of an EGFR-PI3K-Akt-CREB signaling pathway mediated YAP gene expression and YAP nuclear translocation and interaction with the TEA domain (TEAD) transcription factor complex, which led to upregulated expression of two TEAD-dependent genes, the connective tissue growth factor and amphiregulin genes. In a renal proximal tubule cell line, either pharmacologic or genetic inhibition of EGFR, Akt, or CREB blunted YAP expression in response to highglucose treatment. Additionally, knocking down YAP expression by specific siRNA inhibited cell proliferation in response to high glucose or exogenous EGF. Therefore, these results link the Hippo pathway to EGFRmediated renal epithelial injury in diabetes.

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Section: Exposure Of Renal Epithelial Cells Tomentioning

confidence: 99%

Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic Kidney

Chen¹,

Harris

2015

JASN

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“…Both Verteporfin (VP, trade name Visudyne by Novartis) and protoporphyrin IX (PPIX) inhibit the YAP-TEAD complex formation at 10 μM in Co-immunoprecipitation assays (43). VP is a FDA-approved photosensitizer in the photodynamic therapy of neovascular macular degeneration; however, when used as an inhibitor of the YAP-TEAD interaction, light activation is not required (43,44). VP alters YAP conformation when binding to it, and abolished its interaction to TEAD (45).…”

Section: Direct Interruption Of Yap-tead Mediated Transcriptional Actmentioning

confidence: 99%

Drug development against the hippo pathway in mesothelioma

Woodard

Yang

et al. 2017

Transl. Lung Cancer Res.

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“…The administration of verteporfi n, which inhibits YAP by disrupting the YAP-TEAD transcriptional activator complex (Brodowska et al, 2014), had no effect on caspase-3 activation by ethanol (Fig. 3A), nor did YAP-TEAD inhibitor 1 (peptide 17), another YAP inhibitor (Zhang et al, 2014) (Fig.…”

Section: Yap Inhibitors Do Not Affect Apoptotic Cell Death By Ethanolmentioning

confidence: 99%

Restoration of YAP activation rescues HL-1 cardiomyocytes from apoptotic death by ethanol

et al. 2017

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-We reported previously that when mouse atrium-derived HL-1 cardiomyocytes undergo apoptosis upon exposure to 2% ethanol, the cellular cytoskeleton is severely disrupted and the anti-apoptotic transcriptional co-activator Yes-associated protein (YAP) is inactivated. Consistent with our previous observations, the expression of connective tissue growth factor (CTGF), an anti-apoptotic growth factor and a target of YAP, decreases in a time-dependent manner during exposure to 2% ethanol. The restoration of YAP activation rescues the cells from apoptosis: both the retrovirus-mediated expression of constitutively active YAP and the stabilization of the actomyosin cytoskeleton by jasplakinolide prevent cell death. In contrast, YAP inhibitors have no effect on cell death, confirming the inactivation of YAP in ethanol-exposed cells. Thus, a decrease in actin tension and YAP inactivation should be crucially involved in the cytotoxicity of ethanol on HL-1 cardiomyocytes.

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The clinically used photosensitizer Verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation

Cited by 199 publications

References 55 publications

Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic Kidney

Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic Kidney

Drug development against the hippo pathway in mesothelioma

Restoration of YAP activation rescues HL-1 cardiomyocytes from apoptotic death by ethanol

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