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
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Rapid Impact Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Metabolism Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Spotlight on Genomic Analysis of Rare and Understudied Cancers
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • 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
Molecular Cancer Research
Molecular Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Rapid Impact Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Metabolism Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Spotlight on Genomic Analysis of Rare and Understudied Cancers
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Cancer Genes and Networks

Palmitate-Induced IRE1–XBP1–ZEB Signaling Represses Desmoplakin Expression and Promotes Cancer Cell Migration

Aritro Nath, Amrita Oak, Kevin Y. Chen, Irene Li, R. Chauncey Splichal, Jason Portis, Sean Foster, S. Patrick Walton and Christina Chan
Aritro Nath
1Genetics Program, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Aritro Nath
Amrita Oak
2Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin Y. Chen
2Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irene Li
2Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Chauncey Splichal
2Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason Portis
2Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sean Foster
2Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Patrick Walton
2Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christina Chan
1Genetics Program, Michigan State University, East Lansing, Michigan.
2Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
3Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: krischan@egr.msu.edu
DOI: 10.1158/1541-7786.MCR-19-0480 Published February 2021
  • 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

Elevated uptake of saturated fatty acid palmitate is associated with metastatic progression of cancer cells; however, the precise signaling mechanism behind the phenomenon is unclear. The loss of cell adhesion proteins, such as desmoplakin (DSP), is a key driving event in the transformation of cancer cells to more aggressive phenotypes. Here, we investigated the mechanism by which palmitate induces the loss of DSP in liver and breast cancer cells. We propose that palmitate activates the IRE1–XBP1 branch of the endoplasmic reticulum (ER) stress pathway to upregulate the ZEB transcription factor, leading to transcriptional repression of DSP. Using liver and breast cancer cells treated with palmitate, we found loss of DSP leads to increased cell migration independent of E-cadherin. We report that the ZEB family of transcription factors function as direct transcriptional repressors of DSP. CRISPR-mediated knockdown of IRE1 confirmed that the transcription of ZEB, loss of DSP, and enhanced migration in the presence of palmitate is dependent on the IRE1–XBP1 pathway. In addition, by analyzing the somatic expression and copy number variation profiles of over 11,000 tumor samples, we corroborate our hypothesis and establish the clinical relevance of DSP loss via ZEB in human cancers.

Implications: Provides mechanistic link on palmitate-induced activation of IRE1α to cancer cell migration.

Footnotes

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

  • Mol Cancer Res 2021;19:240–8

  • Received May 10, 2019.
  • Revision received April 23, 2020.
  • Accepted October 21, 2020.
  • Published first October 26, 2020.
  • ©2020 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 already have one.
PreviousNext
Back to top
Molecular Cancer Research: 19 (2)
February 2021
Volume 19, Issue 2
  • 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.
Palmitate-Induced IRE1–XBP1–ZEB Signaling Represses Desmoplakin Expression and Promotes Cancer Cell Migration
(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.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Palmitate-Induced IRE1–XBP1–ZEB Signaling Represses Desmoplakin Expression and Promotes Cancer Cell Migration
Aritro Nath, Amrita Oak, Kevin Y. Chen, Irene Li, R. Chauncey Splichal, Jason Portis, Sean Foster, S. Patrick Walton and Christina Chan
Mol Cancer Res February 1 2021 (19) (2) 240-248; DOI: 10.1158/1541-7786.MCR-19-0480

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Palmitate-Induced IRE1–XBP1–ZEB Signaling Represses Desmoplakin Expression and Promotes Cancer Cell Migration
Aritro Nath, Amrita Oak, Kevin Y. Chen, Irene Li, R. Chauncey Splichal, Jason Portis, Sean Foster, S. Patrick Walton and Christina Chan
Mol Cancer Res February 1 2021 (19) (2) 240-248; DOI: 10.1158/1541-7786.MCR-19-0480
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
    • Authors' Disclosures
    • Authors' Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • G9a Promotes Invasion and Metastasis in NSCLCs through FAK
  • Antioxidant NAC Enhances Ex Vivo Culture of Single CTCs
  • Pan-Cancer MYC Activity Inference
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

About MCR

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

Copyright © 2021 by the American Association for Cancer Research.

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

Advertisement