YAP/TAZ as therapeutic targets in cancer

Zanconato, Francesca; Battilana, Giusy; Cordenonsi, Michelangelo; Piccolo, Stefano

doi:10.1016/j.coph.2016.05.002

Cited by 194 publications

(174 citation statements)

References 65 publications

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“…And it plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis [15,17]. Similarly to TGFBR2, most research concerning YAP-1 has been carried out within tumor cells; the roles of YAP-1 in immune cells were relatively poorly known.…”

Section: Discussionmentioning

confidence: 99%

“…Since YAP is a co-activator of TEADs and has no DNA binding site, its regulation on TGFBR2 is TEADs dependent [17]. A TEADs binding site "GGAATG" was detected in the promoter region of TGFBR2 (Fig.…”

Section: Up-regulation Of Tgfbr2 In T Cells Depends On Yap-1/teads Atmentioning

confidence: 99%

“…Within the tumor, YAP-1 itself lacks DNA-binding capacity, and can act as a co-activator when combined with the TEAD family as a transcriptional coactivator [15][16][17]. YAP-1 and its close paralog, TAZ (WWTR1), are the main effectors of the Hippo tumor suppressor pathway [15].…”

Section: Introductionmentioning

confidence: 99%

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YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription

Fan¹,

Gao²,

Rao³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Immunosuppression is one of the hallmarks of cancer; however, its molecular mechanism remains unknown. In the present study, we sought to investigate the expression and activation of yes-associated protein 1 (YAP-1) and its roles in T cells within hepatocellular carcinoma (HCC). Methods: The expression and activation of YAP-1 were accessed by real-time PCR, immunohistochemistry staining, western blot, and flow cytometry. The potential regulation effect of YAP-1 on Regulatory T cells (Tregs) differentiation was predicted using bioinformatics tools and verified by in vitro studies. Results: Significant overexpression and activation of YAP-1 was detected within peripheral blood mononuclear cells and showed positive linear correlation to Treg percentage; it may serve as a valuable indicator of a bad prognosis. Using in vitro studies, we found that overexpression and activation of YAP-1 can promote naïve T cell polarization stimulation to Tregs by increasing the expression of TGFBR2. The YAP-1/TEADs DNA binding site was spotted within the promoter region of TGFBR2 and related to its transcription activity. YAP-1 acted as a co-activator of TGFBR2 transcription by binding directly to the TGFBR2 promoter through TEADs. Conclusion: Overexpression and activation of YAP-1 in HCC T cells can induce immunosuppression by promoting Treg differentiation via transcriptional enhancement of TGFBR2.

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Section: Discussionmentioning

confidence: 99%

Section: Up-regulation Of Tgfbr2 In T Cells Depends On Yap-1/teads Atmentioning

confidence: 99%

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YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription

Fan¹,

Gao²,

Rao³

et al. 2017

Cell Physiol Biochem

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“…It has also been demonstrated that F-actin promotes YAP nuclear translocation and inhibits the Hippo pathway, and that destabilization of F-actin results in the nuclear exportation of YAP (32,33). The clinical use of anti-cytoskeletal therapies has been limited due to toxicity (34). Current therapeutic approaches to target mechanotransduction signals in cancer work through inhibiting Rho-associated kinase (ROCK) signaling (34,35).…”

Section: Rockmentioning

confidence: 99%

“…The clinical use of anti-cytoskeletal therapies has been limited due to toxicity (34). Current therapeutic approaches to target mechanotransduction signals in cancer work through inhibiting Rho-associated kinase (ROCK) signaling (34,35). ROCK inhibition was recently reported to suppress YAP activity in MPM cells harboring LAST2 mutation, suggesting that ROCK could regulate the Hippo pathway through a LATS2-independent mechanism (36).…”

Section: Rockmentioning

confidence: 99%

Drug development against the hippo pathway in mesothelioma

Woodard

Yang

et al. 2017

Transl. Lung Cancer Res.

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ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP

Sun

et al. 2018

FEBS Letters

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Although colorectal cancer (CRC) is a prevalent malignancy of the digestive system, the underlying mechanisms of CRC tumorigenesis are still elusive. Arrestin-related domain-containing protein-3 (ARRDC3) has been reported to promote lysosome-mediated protein degradation. In the present study, we find that the expression of ARRDC3 is downregulated in CRC specimens. Mechanistically, we reveal that ARRDC3 binds and decreases expression of the oncoprotein YAP, the cotranscription factor of the Hippo pathway. The regulation of the Hippo pathway by ARRDC3 is conserved from Drosophila to mammals. Furthermore, we demonstrate that ARRDC3 plays an anti-oncogenic role in CRC progression by promoting YAP degradation. Finally, we show that ARRDC3 increases the sensitivity of CRC cells toward chemotherapeutic drugs. Taken together, our findings point to ARRDC3 as a potential target for CRC treatment.

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YAP/TAZ as therapeutic targets in cancer

Cited by 194 publications

References 65 publications

YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription

YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription

Drug development against the hippo pathway in mesothelioma

ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP

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