Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jun 13;29(6):783-803.
doi: 10.1016/j.ccell.2016.05.005.

YAP/TAZ at the Roots of Cancer

Francesca Zanconato  1 , Michelangelo Cordenonsi  2 , Stefano Piccolo  3
Affiliations
Review

YAP/TAZ at the Roots of Cancer

Francesca Zanconato et al. Cancer Cell. .

Abstract

YAP and TAZ are highly related transcriptional regulators pervasively activated in human malignancies. Recent work indicates that, remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, chemoresistance, and metastasis. YAP/TAZ are sensors of the structural and mechanical features of the cell microenvironment. A number of cancer-associated extrinsic and intrinsic cues conspire to overrule the YAP-inhibiting microenvironment of normal tissues, including changes in mechanotransduction, inflammation, oncogenic signaling, and regulation of the Hippo pathway. Addiction to YAP/TAZ thus potentially represents a central cancer vulnerability that may be exploited therapeutically.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Schematic overview of YAP/TAZ functions in cancer cells.
See text for details.
Figure 2
Figure 2. YAP/TAZ in human tumors.
Tumor types for which epidemiological data and functional evidence of YAP/TAZ activation have been reported.
Figure 3
Figure 3. Inputs regulating YAP/TAZ activity in cancer cells.
See text for details.
Figure 4
Figure 4. The onset of drug resistance is accompanied by YAP/TAZ activation.
(A-C) A) Drug sensitive cancer cells. The mechanism of YAP/TAZ activation in response to molecularly targeted therapies involves cell-autonomous events (B), such as cytoskeletal rearrangements leading to increased mechanosensitivity, as well as cell extrinsic events (C), such as remodeling of the extracellular microenvironment. Possibly, these two mechanisms cooperate to induce YAP/TAZ nuclear accumulation in cancer cells, leading to uncontrolled cell survival and proliferation in spite of drug administration.
See this image and copyright information in PMC

References

    1. Anakk S, Bhosale M, Schmidt VA, Johnson RL, Finegold MJ, Moore DD. Bile acids activate YAP to promote liver carcinogenesis. Cell reports. 2013;5:1060–1069. - PMC - PubMed
    1. Antonescu CR, Le Loarer F, Mosquera JM, Sboner A, Zhang L, Chen CL, Chen HW, Pathan N, Krausz T, Dickson BC, et al. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes, chromosomes & cancer. 2013;52:775–784. - PMC - PubMed
    1. Aragona M, Panciera T, Manfrin A, Giulitti S, Michielin F, Elvassore N, Dupont S, Piccolo S. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell. 2013;154:1047–1059. - PubMed
    1. Azzolin L, Panciera T, Soligo S, Enzo E, Bicciato S, Dupont S, Bresolin S, Frasson C, Basso G, Guzzardo V, et al. YAP/TAZ incorporation in the beta-catenin destruction complex orchestrates the Wnt response. Cell. 2014;158:157–170. - PubMed
    1. Azzolin L, Zanconato F, Bresolin S, Forcato M, Basso G, Bicciato S, Cordenonsi M, Piccolo S. Role of TAZ as mediator of Wnt signaling. Cell. 2012;151:1443–1456. - PubMed

Publication types

MeSH terms

Substances