Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells

PloS One
Zhi-Qiang WangDimcho Bachvarov

Abstract

Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from serous epithelial ovarian cancer (EOC) patients, when compared to primary cultures derived from matched primary (prior to CT) tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic) stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data ...Continue Reading

References

Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·Q WangN A Speck
Jul 15, 1999·Nature Structural Biology·X HuangJ H Bushweller
Dec 22, 1999·The Journal of Biological Chemistry·K HishikawaT Fujii
Aug 19, 2000·In Vitro Cellular & Developmental Biology. Animal·Diane ProvencherA M Mes-Masson
Sep 21, 2000·Journal of the National Cancer Institute·Ignace VergoteJ B Vermorken
Nov 1, 2001·Annual Review of Cell and Developmental Biology·M D Sternlicht, Z Werb
Jan 7, 2003·The Journal of Biological Chemistry·Paula OfekSara Lavi
Jan 18, 2003·International Journal of Cancer. Journal International Du Cancer·Brad StoneBrad H Nelson
Jul 2, 2003·Nature Reviews. Cancer·Roshan Agarwal, Stan B Kaye
Oct 7, 2003·Oncogene·Richard L Momparler
Oct 31, 2003·American Journal of Obstetrics and Gynecology·Jill S Barnholtz-SloanAdnan R Munkarah
Jan 31, 2004·Cell Cycle·Yue ZhangJefferey L Wrana
Feb 21, 2004·Cell Cycle·Estelle Duprez
May 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karen H LuRobert C Bast
May 3, 2005·Nature Reviews. Cancer·Karen BlythJames Neil
Jul 2, 2005·The EMBO Journal·Kiyoshi TamuraShigetaka Kitajima
Aug 5, 2005·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Sabine MaierChristian Piepenbrock
Aug 13, 2005·Cell Cycle·Kentaro KinjoDeepa B Shankar
Apr 22, 2006·Cell Cycle·Chunhong Yan, Douglas D Boyd
Feb 27, 2007·Cell·Peter A Jones, Stephen B Baylin
May 27, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Bernard TêtuDimcho Bachvarov
Jul 4, 2009·Endocrinology·Curt BalchKenneth P Nephew
Aug 4, 2009·Omics : a Journal of Integrative Biology·Shiqian ZhangHao Yu
Aug 18, 2009·Biochimica Et Biophysica Acta·Manish Mani SubramaniamManuel Salto-Tellez
Feb 11, 2010·Blood Cells, Molecules & Diseases·Chelsia Qiuxia WangMotomi Osato
Jun 29, 2010·Blood Cells, Molecules & Diseases·Karen BlythEwan R Cameron
Jul 27, 2010·Journal of Cellular Physiology·Carla CanoJuan L Iovanna
Jan 5, 2011·Sarcoma·J W MartinJ A Squire
Feb 22, 2011·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Annika J BockAnne Cathrine Staff
Feb 24, 2011·Journal of Cellular Physiology·Maria Jose SandiJuan L Iovanna
May 27, 2011·Gynecologic Oncology·Cecilia Wei Lin LeeYoshiaki Ito
Jun 21, 2011·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Aug 23, 2011·Molecular Oncology·Pierre-Luc MercierDimcho Bachvarov
Sep 6, 2011·Journal of Dermatological Science·Toshifumi YamaokaShinichi Sato
Sep 10, 2011·The Journal of Endocrinology·Georgia PapacleovoulouJ Ian Mason
Oct 4, 2011·The Journal of Biological Chemistry·K Adam MorrowLalita A Shevde
Mar 6, 2012·Journal of Cellular Biochemistry·Daniel J PurcellMichael R Stallcup
Mar 21, 2012·British Journal of Pharmacology·C J Fowler
May 9, 2012·Gynecologic Oncology·S Alouini
May 30, 2012·Laboratory Investigation; a Journal of Technical Methods and Pathology·Dong-Feng NiuRyohei Katoh
Nov 15, 2012·Journal of Cellular Biochemistry·Cornelia Johanna Franziska Scheitz, Tudorita Tumbar
Mar 9, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hong LiJian-Ping Xu
Feb 1, 2013·European Journal of Trauma and Emergency Surgery : Official Publication of the European Trauma Society·Y XuH-H Yang

Citations

Mar 18, 2015·International Journal of Oncology·Chunyan WenHaifeng Li
Jul 19, 2015·Gynecologic Oncology·Samir H BarghoutYangXin Fu
Aug 16, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiaolong XuTingting Ren
Jul 18, 2019·International Journal of Molecular Sciences·Huachen ChenYangXin Fu
Mar 15, 2015·Cancer Research·Valentina SancisiAlessia Ciarrocchi

Related Concepts

Related Feeds

Cancer Epigenetics & Metabolism (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 the relationship between cell metabolism, epigenetics and tumor differentiation.

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.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Cancer Epigenetics (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. Here is the latest research on cancer epigenetics.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

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

Cancer Epigenetics

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. Here is the latest research on cancer epigenetics.

Cancer Epigenetics and Metabolism (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 the relationship between cell metabolism, epigenetics and tumor differentiation.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

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 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.

Cancer Epigenetics and Senescence (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 be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.