Prostate-Derived Ets Factor (PDEF) Inhibits Metastasis by Inducing Epithelial/Luminal Phenotype in Prostate Cancer Cells

Molecular Cancer Research : MCR
Fengtian WangHari K Koul

Abstract

Metastasis is the primary cause of prostate cancer morbidity and mortality. Our previous studies revealed that Sam pointed domain ETS transcription factor, a.k.a. prostate-derived ETS factor (SPDEF/PDEF), inhibits prostate cancer metastasis. However, the mechanism is still unclear. In this study, using microarray and gene set enrichment analysis, we discovered that PDEF upregulated epithelial/luminal differentiation-related genes while it suppressed stemness and epithelial-to-mesenchymal transition-related genes, especially Twist1. We also observed loss of PDEF and gain of Twist1 expression during prostate cancer progression in the TRAMP mouse model. Moreover, Twist1 knockdown resulted in upregulation of PDEF expression, suggesting a reciprocal regulation between PDEF and Twist1. Mechanistically, our ChIP-seq analysis revealed that PDEF directly regulated cytokeratin 18 (CK18) transcription through the GGAT motif within its putative promoter region. CK18 knockdown resulted in increased expression of Twist1, suggesting that PDEF regulated Twist1 in part via CK18. Our analysis of multiple clinical prostate cancer cohorts revealed an inverse relationship between PDEF expression and tumor grade, tumor metastasis, and poor patient s...Continue Reading

References

Nov 1, 1979·Journal of Steroid Biochemistry·G PointisL Cedard
Jun 3, 2000·Human Pathology·L BubendorfM J Mihatsch
Oct 6, 2000·Genes & Development·C Abate-Shen, M M Shen
Jan 5, 2002·Differentiation; Research in Biological Diversity·Y WangG Cunha
Apr 23, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ute WoelfleKlaus Pantel
Oct 23, 2004·Nucleic Acids Research·Peter C HollenhorstBarbara J Graves
Jun 17, 2005·Cancer Research·Wai Kei KwokXianghong Wang
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Mar 10, 2007·The Journal of Clinical Investigation·Kwon-Sik ParkJeffrey A Whitsett
Apr 4, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D Andrew LoblawUNKNOWN American Society of Clinical Oncology
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Oct 23, 2008·Nucleic Acids Research·Tanya BarrettRon Edgar
Mar 18, 2010·BMC Medical Genomics·Andrea SbonerOve Andrén
Jun 3, 2010·The EMBO Journal·Gong-Hong WeiJussi Taipale
May 11, 2011·Nature Reviews. Clinical Oncology·Justin SturgeJonathan Waxman
Jul 19, 2011·Cancer Letters·Joshua J Steffan, Hari K Koul
Jul 5, 2012·The Journal of Biological Chemistry·Joshua J SteffanHari K Koul
Aug 29, 2013·Molecular Cancer Research : MCR·Rajendra P GajulaPhuoc T Tran
Oct 15, 2013·Cell·Denes HniszRichard A Young
Jan 15, 2014·Cancer Metastasis Reviews·Rhonda L BittingAndrew J Armstrong
Feb 14, 2014·American Journal of Physiology. Renal Physiology·Sweaty KoulHari K Koul
Mar 25, 2014·Endocrine-related Cancer·Delila Gasi TandefeltJan Trapman
May 21, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·David J DeGraffRobert J Matusik
Jun 6, 2014·International Journal of Oncology·In-Je KimChaeyong Jung
Oct 7, 2015·Trends in Cell Biology·Xin Ye, Robert A Weinberg
Jan 9, 2016·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
May 18, 2016·The Journal of Steroid Biochemistry and Molecular Biology·Leanne K ArcherNorman J Maitland
Feb 12, 2017·Cell·Arthur W LambertRobert A Weinberg
Apr 22, 2017·Oncotarget·Micaela MontanariGaetano Facchini

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.