Regulation of TEAD Transcription Factors in Cancer Biology

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Transcriptional enhanced associate domain (TEAD) transcription factors play important roles during development, cell proliferation, regeneration, and tissue homeostasis. TEAD integrates with and coordinates various signal transduction pathways including Hippo, Wnt, transforming growth factor beta (TGFβ), and epidermal growth factor receptor (EGFR) pathways. TEAD deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC, and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key transcription factors of the Hippo pathway. Therefore, most studies are focused on the Hippo kinases and YAP/TAZ, whereas the Hippo-dependent and Hippo-independent regulators and regulations governing TEAD only emerged recently. Deregulation of the TEAD transcriptional output plays important roles in tumor progression and serves as a prognostic biomarker due to high correlation with clinicopathological parameters in human malignancies. In addition, discovering the molecular mechanisms of TEAD, such as post-translational modifications and nucleocytoplasmic shuttling, represents an important means of modulating TEAD transcriptional activity. Collectively, this review highlights the role of TEAD in multistep-tumorigenesis by interacting with upstream oncogenic signaling pathways and controlling downstream target genes, which provides unprecedented insight and rationale into developing TEAD-targeted anticancer therapeutics.

Related collections

Most cited references 132

Record: found
Abstract: found
Article: not found

Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP.

Yi Liu-Chittenden, Bo Huang, Joong Sup Shim … (2012)

The Drosophila TEAD ortholog Scalloped is required for Yki-mediated overgrowth but is largely dispensable for normal tissue growth, suggesting that its mammalian counterpart may be exploited for selective inhibition of oncogenic growth driven by YAP hyperactivation. Here we test this hypothesis genetically and pharmacologically. We show that a dominant-negative TEAD molecule does not perturb normal liver growth but potently suppresses hepatomegaly/tumorigenesis resulting from YAP overexpression or Neurofibromin 2 (NF2)/Merlin inactivation. We further identify verteporfin as a small molecule that inhibits TEAD-YAP association and YAP-induced liver overgrowth. These findings provide proof of principle that inhibiting TEAD-YAP interactions is a pharmacologically viable strategy against the YAP oncoprotein.

0 comments Cited 584 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response.

Luca Azzolin, Tito Panciera, Sandra Soligo … (2014)

The Hippo transducers YAP/TAZ have been shown to play positive, as well as negative, roles in Wnt signaling, but the underlying mechanisms remain unclear. Here, we provide biochemical, functional, and genetic evidence that YAP and TAZ are integral components of the β-catenin destruction complex that serves as cytoplasmic sink for YAP/TAZ. In Wnt-ON cells, YAP/TAZ are physically dislodged from the destruction complex, allowing their nuclear accumulation and activation of Wnt/YAP/TAZ-dependent biological effects. YAP/TAZ are required for intestinal crypt overgrowth induced by APC deficiency and for crypt regeneration ex vivo. In Wnt-OFF cells, YAP/TAZ are essential for β-TrCP recruitment to the complex and β-catenin inactivation. In Wnt-ON cells, release of YAP/TAZ from the complex is instrumental for Wnt/β-catenin signaling. In line, the β-catenin-dependent maintenance of ES cells in an undifferentiated state is sustained by loss of YAP/TAZ. This work reveals an unprecedented signaling framework relevant for organ size control, regeneration, and tumor suppression. Copyright © 2014 Elsevier Inc. All rights reserved.

0 comments Cited 486 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mutations in GNA11 in uveal melanoma.

Catherine D. Van Raamsdonk, Klaus G. Griewank, Michelle Crosby … (2010)

Uveal melanoma is the most common intraocular cancer. There are no effective therapies for metastatic disease. Mutations in GNAQ, the gene encoding an alpha subunit of heterotrimeric G proteins, are found in 40% of uveal melanomas. We sequenced exon 5 of GNAQ and GNA11, a paralogue of GNAQ, in 713 melanocytic neoplasms of different types (186 uveal melanomas, 139 blue nevi, 106 other nevi, and 282 other melanomas). We sequenced exon 4 of GNAQ and GNA11 in 453 of these samples and in all coding exons of GNAQ and GNA11 in 97 uveal melanomas and 45 blue nevi. We found somatic mutations in exon 5 (affecting Q209) and in exon 4 (affecting R183) in both GNA11 and GNAQ, in a mutually exclusive pattern. Mutations affecting Q209 in GNA11 were present in 7% of blue nevi, 32% of primary uveal melanomas, and 57% of uveal melanoma metastases. In contrast, we observed Q209 mutations in GNAQ in 55% of blue nevi, 45% of uveal melanomas, and 22% of uveal melanoma metastases. Mutations affecting R183 in either GNAQ or GNA11 were less prevalent (2% of blue nevi and 6% of uveal melanomas) than the Q209 mutations. Mutations in GNA11 induced spontaneously metastasizing tumors in a mouse model and activated the mitogen-activated protein kinase pathway. Of the uveal melanomas we analyzed, 83% had somatic mutations in GNAQ or GNA11. Constitutive activation of the pathway involving these two genes appears to be a major contributor to the development of uveal melanoma. (Funded by the National Institutes of Health and others.).

0 comments Cited 456 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Cells

Journal ID (iso-abbrev): Cells

Journal ID (publisher-id): cells

Title: Cells

Publisher: MDPI

ISSN (Electronic): 2073-4409

Publication date (Electronic): 17 June 2019

Publication date Collection: June 2019

Volume: 8

Issue: 6

Electronic Location Identifier: 600

Affiliations

[1 ]Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea; huhhb621@ 123456yonsei.ac.kr (H.D.H.); dhk1107@ 123456yonsei.ac.kr (D.H.K.)

[2 ]Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Korea

Author notes

[* ]Correspondence: jhsol33@ 123456pusan.ac.kr (H.-S.J.); hwp003@ 123456yonsei.ac.kr (H.W.P.); Tel.: +82-51-510-8461 (H.-S.J.); +82-2-2123-2698 (H.W.P.)

Author information

Han-Sol Jeong https://orcid.org/0000-0001-9452-3010

Article

Publisher ID: cells-08-00600

DOI: 10.3390/cells8060600

PMC ID: 6628201

PubMed ID: 31212916

SO-VID: 2b0cd793-7381-45bc-8cf3-8e20e3c53169

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Regulation of TEAD Transcription Factors in Cancer Biology

Read this article at

Abstract

Related collections

Stress signalling in stem cells

Most cited references 132

Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP.

YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response.

Mutations in GNA11 in uveal melanoma.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 366

Cited by 95

Most referenced authors 3,541