Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Reviewing
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Discovery
Cancer Discovery
  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Reviewing
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

Research Watch

Peritumoral YAP and TAZ Expression Suppresses Tumor Growth in Mice

DOI: 10.1158/2159-8290.CD-RW2019-180 Published January 2020
  • Article
  • Info & Metrics
  • PDF
Loading
  • Major Finding: Peritumoral expression of Hippo-pathway members YAP and TAZ restricts liver-tumor growth in mice.

  • Mechanism: Peritumoral YAP and TAZ activation triggered nonapoptotic programmed cell death in the tumor cells.

  • Impact: If present in humans, this may hinder the effectiveness of future YAP- or TAZ-targeting drugs.


Embedded Image

Hyperactivation of the Hippo signaling pathway via upregulation of its two downstream effectors, the transcriptional coactivators YAP and TAZ, has been shown to promote tumorigenesis. In a mouse model of intrahepatic cholangiocarcinoma, Moya, Castaldo, Van den Mooter, Soheily, and colleagues detected large amounts of YAP and TAZ in tumor cells, as expected. However, there was also YAP accumulation in peritumoral hepatocytes and an increase in expression of classic YAP targets along with an increase in a proliferation marker in these cells. Deletion of Yap and the homologous Taz in normal hepatocytes but not tumor cells increased tumor-cell proliferation, resulting in increased tumor burden, implying that YAP and TAZ in peritumoral hepatocytes normally function to restrict tumor growth. Consistent with this notion, condtional deletion of the genes encoding the YAP and TAZ inhibitors LATS1 and LATS2 in peritumoral hepatocytes substantially diminished tumor growth, and conditional overexpression of a constitutively active form of human YAP in the normal liver cells caused tumor regression in the mice. Further investigation revealed that activation of YAP or TAZ in peritumoral hepatocytes exerted its antitumor effects by inducing nonapoptotic programmed cell death in the tumor cells. Notably, the tumor cells required YAP and TAZ for survival only when the surrounding cells possessed wild-type YAP and TAZ. The tumor-suppressive effects of peritumoral YAP and TAZ extended to a mouse model of hepatocellular carcinoma as well as a mouse model of aggressive, NRAS-mutant melanoma that had metastasized to the liver. Together, these results suggest that cell competition akin to that originally detailed in Drosophila may be at work; specifically, the dependence of tumor cells on YAP and TAZ was specified by the levels of YAP and TAZ in the surrounding normal tissue. Given the interest in developing YAP- and TAZ-targeting drugs, further work to determine whether this effect is present in humans is needed, as it implies that systemic inhibition of YAP and TAZ may actually have protumorigenic effects.

Moya IM, Castaldo SA, Van den Mooter L, Soheily S, Sansores-Garcia L, Jacobs J, et al. Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice. Science;366:1029–34.

Notes

Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.

  • ©2020 American Association for Cancer Research.
View Abstract
PreviousNext
Back to top
Cancer Discovery: 10 (1)
January 2020
Volume 10, Issue 1
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Discovery article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Peritumoral YAP and TAZ Expression Suppresses Tumor Growth in Mice
(Your Name) has forwarded a page to you from Cancer Discovery
(Your Name) thought you would be interested in this article in Cancer Discovery.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Peritumoral YAP and TAZ Expression Suppresses Tumor Growth in Mice
Cancer Discov January 1 2020 (10) (1) 14; DOI: 10.1158/2159-8290.CD-RW2019-180

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Peritumoral YAP and TAZ Expression Suppresses Tumor Growth in Mice
Cancer Discov January 1 2020 (10) (1) 14; DOI: 10.1158/2159-8290.CD-RW2019-180
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Notes
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

Research Watch

  • Structures Identify Selpercatinib and Pralsetinib Resistance Mechanisms
  • Computational Tool Characterizes Previously Unidentified Tumor Subtypes
  • Deep Learning Algorithm Aids Breast Cancer Detection by Mammography
Show more Research Watch

Signaling

  • The STRIPAK Complex Regulates the Hippo Kinase Cascade
  • RAF Binding Preferences Dictate RAS-Mediated Tumorigenesis
Show more Signaling
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • OnlineFirst
  • Current Issue
  • Past Issues

Info For

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Discovery

  • About the Journal
  • Editors
  • Journal Sections
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Discovery
eISSN: 2159-8290
ISSN: 2159-8274

Advertisement