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

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Rapid Impact Archive
    • Meeting Abstracts
    • Collections
      • Metabolism Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
  • 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
Molecular Cancer Research
Molecular Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Rapid Impact Archive
    • Meeting Abstracts
    • Collections
      • Metabolism Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
Cancer Genes and Networks

Paracrine Interaction of Cancer Stem Cell Populations Is Regulated by the Senescence-Associated Secretory Phenotype (SASP)

Angelica M. Lagunas, Marybeth Francis, Nisha B. Maniar, Gergana Nikolova, Jianchun Wu and David L. Crowe
Angelica M. Lagunas
University of Illinois Cancer Center, Chicago, Illinois.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marybeth Francis
University of Illinois Cancer Center, Chicago, Illinois.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nisha B. Maniar
University of Illinois Cancer Center, Chicago, Illinois.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gergana Nikolova
University of Illinois Cancer Center, Chicago, Illinois.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianchun Wu
University of Illinois Cancer Center, Chicago, Illinois.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David L. Crowe
University of Illinois Cancer Center, Chicago, Illinois.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dlcrowe@uic.edu
DOI: 10.1158/1541-7786.MCR-18-1356 Published July 2019
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below.

Abstract

Dyskeratosis congenita is a telomere DNA damage syndrome characterized by defective telomere maintenance, bone marrow failure, and increased head and neck cancer risk. The Pot1b−/−;Terc+/− mouse exhibits some features of dyskeratosis congenita, but head and neck cancer was not reported in this model. To model the head and neck cancer phenotype, we created unique Pot1b- and p53-null–mutant models which allow genetic lineage tracing of two distinct stem cell populations. Loss of Pot1b expression depleted stem cells via ATR/Chk1/p53 signaling. Tumorigenesis was inhibited in Pot1b−/−;p53+/+ mice due to cellular senescence. Pot1b−/−;p53−/− tumors also exhibited senescence, but proliferated and metastasized with expansion of Lgr6+ stem cells indicative of senescence-associated secretory phenotype. Selective depletion of the small K15+ stem cell fraction resulted in reduction of Lgr6+ cells and inhibition of tumorigenesis via senescence. Gene expression studies revealed that K15+ cancer stem cells regulate Lgr6+ cancer stem cell expansion via chemokine signaling. Genetic ablation of the chemokine receptor Cxcr2 inhibited cancer stem cell expansion and tumorigenesis via senescence. The effects of chemokines were primarily mediated by PI3K signaling, which is a therapeutic target in head and neck cancer.

Implications: Paracrine interactions of cancer stem cell populations impact therapeutic options and patient outcomes.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).

  • Mol Cancer Res 2019;17:1480–92

  • Received December 22, 2018.
  • Revision received March 25, 2019.
  • Accepted April 25, 2019.
  • Published first May 1, 2019.
  • ©2019 American Association for Cancer Research.
View Full Text

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't.
PreviousNext
Back to top
Molecular Cancer Research: 17 (7)
July 2019
Volume 17, Issue 7
  • 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 Molecular Cancer Research 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.
Paracrine Interaction of Cancer Stem Cell Populations Is Regulated by the Senescence-Associated Secretory Phenotype (SASP)
(Your Name) has forwarded a page to you from Molecular Cancer Research
(Your Name) thought you would be interested in this article in Molecular Cancer Research.
Citation Tools
Paracrine Interaction of Cancer Stem Cell Populations Is Regulated by the Senescence-Associated Secretory Phenotype (SASP)
Angelica M. Lagunas, Marybeth Francis, Nisha B. Maniar, Gergana Nikolova, Jianchun Wu and David L. Crowe
Mol Cancer Res July 1 2019 (17) (7) 1480-1492; DOI: 10.1158/1541-7786.MCR-18-1356

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Paracrine Interaction of Cancer Stem Cell Populations Is Regulated by the Senescence-Associated Secretory Phenotype (SASP)
Angelica M. Lagunas, Marybeth Francis, Nisha B. Maniar, Gergana Nikolova, Jianchun Wu and David L. Crowe
Mol Cancer Res July 1 2019 (17) (7) 1480-1492; DOI: 10.1158/1541-7786.MCR-18-1356
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • SRSF2 Regulates MDM2 Splicing
  • CARMIL3 Regulates Tumor Metastasis
  • PI3K Modulation of MHC Expression
Show more Cancer Genes and Networks
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Rapid Impact Archive
  • Meeting Abstracts

Information for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About MCR

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2019 by the American Association for Cancer Research.

Molecular Cancer Research
eISSN: 1557-3125
ISSN: 1541-7786

Advertisement