Yes-associated protein promotes tumour development in luminal epithelial derived breast cancer

Wang, Xiaodan; Song, Lili; Ou, Qishui

doi:10.1016/j.ejca.2011.10.001

Cited by 95 publications

(97 citation statements)

References 17 publications

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“…YAP has been demonstrated as a driving oncogene on amplicon 11q22, which is amplified in several human tumors (37). Upregulation of YAP and its nuclear localization strongly correlate with poor prognosis and tumor progression in multiple cancers, including breast (38), lung, colorectal, ovarian, and liver carcinomas (39). Overexpression of YAP in a conditional YAP transgenic mouse model led to tissue overgrowth and tumorigenesis (40).…”

Section: Significancementioning

confidence: 99%

Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility

Wang

et al. 2013

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

273

284

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Expression of receptor for hyaluronan-mediated motility (RHAMM), a breast cancer susceptibility gene, is tightly controlled in normal tissues but elevated in many tumors, contributing to tumorigenesis and metastases. However, how the expression of RHAMM is regulated remains elusive. Statins, inhibitors of mevalonate metabolic pathway widely used for hypercholesterolemia, have been found to also have antitumor effects, but little is known of the specific targets and mechanisms. Moreover, Hippo signaling pathway plays crucial roles in organ size control and cancer development, yet its downstream transcriptional targets remain obscure. Here we show that RHAMM expression is regulated by mevalonate and Hippo pathways converging onto Yes-associated protein (YAP)/TEAD, which binds RHAMM promoter at specific sites and controls its transcription and consequently breast cancer cell migration and invasion (BCCMI); and that simvastatin inhibits BCCMI via targeting YAP-mediated RHAMM transcription. Required for ERK phosphorylation and BCCMI, YAP-activated RHAMM transcription is dependent on mevalonate and sensitive to simvastatin, which modulate RHAMM transcription by modulating YAP phosphorylation and nuclear-cytoplasmic localization. Further, modulation by mevalonate/simvastatin of YAP-activated RHAMM transcription requires geranylgeranylation, Rho GTPase activation, and actin cytoskeleton rearrangement, but is largely independent of MST and LATS kinase activity. These findings from in vitro and in vivo investigations link mevalonate and Hippo pathways with RHAMM as a downstream effector, a YAP-transcription and simvastatin-inhibition target, and a cancer metastasis mediator; uncover a mechanism regulating RHAMM expression and cancer metastases; and reveal a mode whereby simvastatin exerts anticancer effects; providing potential targets for cancer therapeutic agents.

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Section: Significancementioning

confidence: 99%

Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility

Wang

et al. 2013

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

273

284

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“…For instance, the extent of nuclear TAZ or YAP levels corresponds with breast cancer tumor grade (2)(3)(4). In breast cancer cells, enhanced nuclear TAZ and YAP levels promote oncogenic transformation and endow cells with tumorigenic properties, including the ability to proliferate, subvert apoptotic cues, migrate, invade, and grow under anchorage-independent conditions (5-9).…”

mentioning

confidence: 99%

The Transcriptional Regulators TAZ and YAP Direct Transforming Growth Factor β-induced Tumorigenic Phenotypes in Breast Cancer Cells

Hiemer

Szymaniak

Varelas

2014

Journal of Biological Chemistry

205

190

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Background:The TGF␤ and Hippo pathways are dysregulated in metastatic breast cancers. Results: TGF␤-induced cues and nuclear TAZ/YAP converge at the transcriptional level to control gene expression important for tumorigenesis. Conclusion: TAZ/YAP are required to promote TGF␤-induced tumorigenic phenotypes in breast cancer cells. Significance: Our study reveals novel cross-talk between the TGF␤ pathway and TAZ/YAP in late-stage breast cancers.

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“…2014; Consistently, a lot of human cancers show overexpression or hyperactivation of nuclear YAP or TAZ or downregulation of Lasts1/2, Mst1/2 or Sav1 function (Dong et al, 2007;Hall et al, 2010;Jiang et al, 2006;Matsuura et al, 2011;Muramatsu et al, 2011;Nallet-Staub et al, 2013;Quan et al, 2014;Seidel et al, 2007;Steinhardt et al, 2008;Su et al, 2012;Takahashi et al, 2005;Wang et al, 2012;Wang et al, 2010;Wierzbicki et al, 2013;Xu et al, 2011;Xu et al, 2009;Yuen et al, 2013;Zender et al, 2006;Zhao et al, 2007;Zhou Z et al, 2011) see also table 4. Moreover, overexpression or hyperactivation of YAP and TAZ have been associated with poor prognosis and shorter survival times for patients in several human cancers (Hall et al, 2010;Liu JH et al, 2013;Muramatsu et al, 2011;Wang et al, 2010;Xu et al, 2009;Zhang et al, 2011).…”

Section: The Hippo Kinase Pathway: a Master Regulator Of Proliferationmentioning

confidence: 92%

The Hippo Kinase Pathway: a master regulator of proliferation, development and differentiation

Lo¹,

Strano²,

Blandino³

2014

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Hippo signaling transduction pathway is widely conserved through evolution and controls cell growth, homeostasis, apoptosis, commitment, differentiation and senescence. It consists of a conserved kinase cascade whose final targets are the transcriptional coactivator Yorkie (Yki) in Drosophila and the homologues YAP and TAZ in mammals. These transcriptional coactivators are unable to bind DNA per se, and can regulate the activity of their target genes only in association with transcription factors. In Drosophila, Yki associates with the transcription factors Sd and Hth regulating pro-proliferative and anti-apoptotic genes. In mammals instead, YAP/TAZ can associate with several distinct transcription factors. This depends from the type of signals to which cells are subjected, the cell type and the developmental stage. The transcriptional outcome resulting from this association can be either pro-apoptotic or pro-proliferative. Hippo pathway dysregulation has been associated with several pathologic conditions (tissue overgrowth, developmental defects and cancer). In particular, solid tumors show an upregulation or hyperactivation of YAP/TAZ, while several hematologic tumors are associated with YAP downregulation. This might suggest that the Hippo pathway holds the potential to be an attractive target for novel therapeutic approaches for cancer.

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Yes-associated protein promotes tumour development in luminal epithelial derived breast cancer

Cited by 95 publications

References 17 publications

Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility

Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility

The Transcriptional Regulators TAZ and YAP Direct Transforming Growth Factor β-induced Tumorigenic Phenotypes in Breast Cancer Cells

The Hippo Kinase Pathway: a master regulator of proliferation, development and differentiation

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