TNFα signaling exposes latent estrogen receptor binding sites to alter the breast cancer cell transcriptome.

Molecular Cell
Hector L FrancoW Lee Kraus

Abstract

The interplay between mitogenic and proinflammatory signaling pathways plays key roles in determining the phenotypes and clinical outcomes of breast cancers. Using GRO-seq in MCF-7 cells, we defined the immediate transcriptional effects of crosstalk between estradiol (E2) and TNFα, identifying a large set of target genes whose expression is rapidly altered with combined E2 + TNFα treatment, but not with either agent alone. The pleiotropic effects on gene transcription in response to E2 + TNFα are orchestrated by extensive remodeling of the ERα enhancer landscape in an NF-κB- and FoxA1-dependent manner. In addition, expression of the de novo and synergistically regulated genes is strongly associated with clinical outcomes in breast cancers. Together, our genomic and molecular analyses indicate that TNFα signaling, acting in pathways culminating in the redistribution of NF-κB and FoxA1 binding sites across the genome, creates latent ERα binding sites that underlie altered patterns of gene expression and clinically relevant cellular responses.

References

Mar 1, 2005·Trends in Endocrinology and Metabolism : TEM·Demetrios Kalaitzidis, Thomas D Gilmore
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Mar 31, 2010·Clinical Reviews in Allergy & Immunology·Melissa Cunningham, Gary Gilkeson
Dec 15, 2010·Nature Genetics·Antoni HurtadoJason S Carroll
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Mar 30, 2011·PloS One·Markus RingnérJohan Staaf
Jul 14, 2011·Genome Research·Nagesha A S RaoHendrik G Stunnenberg
Jul 21, 2011·Nature Immunology·Yinon Ben-Neriah, Michael Karin
Apr 18, 2012·Genome Research·Housheng Hansen HeX Shirley Liu
Jan 19, 2013·Science·Lisa M CoussensA Karolina Palucka
Jan 22, 2013·Cell·Renato OstuniGioacchino Natoli
May 3, 2013·Genome Research·Nasun HahW Lee Kraus
Jul 25, 2013·Nature Reviews. Clinical Oncology·Michail Ignatiadis, Christos Sotiriou
Mar 13, 2014·Nature Reviews. Genetics·Daria ShlyuevaAlexander Stark

❮ Previous
Next ❯

Citations

Sep 24, 2015·Breast Cancer Research : BCR·Meliha MehmetiKarin Leandersson
Jun 4, 2016·Molecular Cell·Kenneth S ZaretMakiko Iwafuchi-Doi
Oct 17, 2017·Nucleic Acids Research·Yehoshua EnukaYosef Yarden
Jan 24, 2018·Nature Genetics·Julie DonagheyAlexander Meissner
Apr 26, 2018·Endocrine-related Cancer·Erin E SwinsteadGordon L Hager
Nov 22, 2018·Molecular Biology of the Cell·Miriam V GutschowMarkus W Covert
Jan 31, 2018·Nature Ecology & Evolution·Charles G DankoAdam Siepel
Aug 5, 2016·Molecular Endocrinology·Marjolein DroogWilbert Zwart
Aug 14, 2019·PloS One·Murugesan PalaniappanCristian Coarfa
Feb 9, 2017·Menopause : the Journal of the North American Menopause Society·Christopher M RipperdaRuth Ann Word
Jul 28, 2016·The Journal of Clinical Endocrinology and Metabolism·Lu GaoCarole R Mendelson
Jan 23, 2016·The Journal of Biological Chemistry·Yichun QiaoKarin Dahlman-Wright
Nov 21, 2018·Life Science Alliance·Melissa BertoDidier Picard
Apr 19, 2019·Nature·Yasuhiro SaitoSenthil K Muthuswamy
Jan 15, 2016·Briefings in Bioinformatics·Sebastian SteinhauserCarl Herrmann
May 26, 2017·Physiological Reviews·Jean-Francois ArnalJohn Katzenellenbogen
Apr 25, 2018·Cellular and Molecular Life Sciences : CMLS·Luca FagnocchiAlessio Zippo
Feb 21, 2019·British Journal of Cancer·Michael J G MilevskiyMelissa A Brown
Jun 11, 2019·Frontiers in Endocrinology·Aradhana RaniJohn Murphy
Mar 6, 2019·Nature Structural & Molecular Biology·Sreejith J NairMichael G Rosenfeld
Feb 23, 2020·Journal of Mammary Gland Biology and Neoplasia·Albana GattelliSabrina A Vallone
Feb 6, 2020·Endocrine-related Cancer·Phungern KhongthongJoanne Edwards
Jun 10, 2020·Nature Structural & Molecular Biology·Vittorio Sartorelli, Shannon M Lauberth

❮ Previous
Next ❯

Related Concepts

Related Feeds

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.