AP-1-mediated chromatin looping regulates ZEB2 transcription: new insights into TNFα-induced epithelial-mesenchymal transition in triple-negative breast cancer

Oncotarget
Yichun QiaoKarin Dahlman-Wright

Abstract

The molecular determinants of malignant cell behaviour in triple-negative breast cancer (TNBC) are poorly understood. Recent studies have shown that regulators of epithelial-mesenchymal transition (EMT) are potential therapeutic targets for TNBC. In this study, we demonstrate that the inflammatory cytokine TNFα induces EMT in TNBC cells via activation of AP-1 signaling and subsequently induces expression of the EMT regulator ZEB2. We also show that TNFα activates both the PI3K/Akt and MAPK/ERK pathways, which act upstream of AP-1. We further investigated in detail AP-1 regulation of ZEB2 expression. We show that two ZEB2 transcripts derived from distinct promoters are both expressed in breast cancer cell lines and breast tumor samples. Using the chromosome conformation capture assay, we demonstrate that AP-1, when activated by TNFα, binds to a site in promoter 1b of the ZEB2 gene where it regulates the expression of both promoter 1b and 1a, the latter via mediating long range chromatin interactions. Overall, this work provides a plausible mechanism for inflammation-induced metastatic potential in TNBC, involving a novel regulatory mechanism governing ZEB2 isoform expression.

References

May 4, 2002·Nature Cell Biology·Eitan Shaulian, Michael Karin
Nov 30, 2005·Nucleic Acids Research·Cindy VandewalleGeert Berx
Jan 25, 2006·Trends in Genetics : TIG·Thomas A Hughes
Feb 24, 2006·Nature Reviews. Molecular Cell Biology·Jean Paul Thiery, Jonathan P Sleeman
Mar 29, 2006·The Journal of Cell Biology·Jonathan M LeeErik W Thompson
Sep 26, 2007·Cancer Science·Shinobu UmemuraYutaka Tokuda
Feb 7, 2008·The Journal of Biological Chemistry·Daniella A BabuRaghavendra G Mirmira
Jun 10, 2008·Developmental Cell·Jing Yang, Robert A Weinberg
Aug 5, 2008·Biochimica Et Biophysica Acta·Stephan Kadauke, Gerd A Blobel
Mar 6, 2009·Nature Reviews. Cancer·Kornelia Polyak, Robert A Weinberg
Apr 4, 2009·Nature Reviews. Cancer·Frances Balkwill
Nov 26, 2009·Nature Cell Biology·Ulrich WellnerThomas Brabletz
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
Dec 22, 2009·American Journal of Clinical Oncology·Anthony D Elias
Jan 12, 2010·Cellular Signalling·Eitan Shaulian
Aug 18, 2010·Current Medicinal Chemistry·Loris Bertazza, Simone Mocellin
Dec 17, 2010·Breast Cancer Research and Treatment·Sumanta Kumar PalMark Pegram
Nov 2, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christoph KahlertJürgen Weitz
Jun 19, 2012·Annual Review of Genomics and Human Genetics·Samin A Sajan, R David Hawkins
Sep 8, 2012·Nature·Amartya SanyalJob Dekker
Dec 25, 2012·International Journal of Molecular Sciences·Valentina PileczkiIoana Berindan-Neagoe
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck

❮ Previous
Next ❯

Citations

Jan 13, 2016·Journal of Experimental & Clinical Cancer Research : CR·Hiroshi HyakusokuNobuhiko Oridate
Nov 19, 2017·Molecular Cancer·Ruobing JiaXianqun Fan
Aug 28, 2020·Frontiers in Bioengineering and Biotechnology·Steven N SteinwayDeok-Ho Kim
Dec 28, 2018·Human Molecular Genetics·Reut Bar YaacovRamon Y Birnbaum
Jul 27, 2018·Veterinary and Comparative Oncology·Pedro L P XavierHeidge Fukumasu
May 12, 2020·Frontiers in Oncology·María Florencia MercoglianoRoxana Schillaci
Jan 23, 2016·The Journal of Biological Chemistry·Yichun QiaoKarin Dahlman-Wright
Aug 30, 2018·Cell Death and Differentiation·Cecilia BattistelliCarla Cicchini
Jul 14, 2019·Molecular Cancer Research : MCR·Claire TolzaIsabelle Jariel-Encontre
Jan 5, 2020·Cellular Oncology (Dordrecht)·Daniel CruceriuIoana Berindan-Neagoe
Mar 3, 2021·Cancer Letters·Dandan SongCecilia Williams
Apr 30, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Fabienne BejjaniIsabelle Jariel-Encontre

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transfection
immunoprecipitation

Software Mentioned

Hi

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.

Breast Cancer Triple-N

Breast cancer cells have receptors for estrogen, progesterone, HER2 receptors (also called ERBB2). Triple-negative breast cancers do not have any of these receptors. Here are the latest discoveries pertaining to triple-negative breast cancers.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Related Papers

La Revue du praticien
Anne Vincent-Salomon
International Journal of Breast Cancer
Quyen D ChuThelma Hurd
Clinical Journal of Oncology Nursing
Debra L Winkeljohn
© 2021 Meta ULC. All rights reserved