Identification of ribonucleotide reductase M2 as a potential target for pro-senescence therapy in epithelial ovarian cancer

Cell Cycle
Katherine M AirdRugang Zhang


Epithelial ovarian cancer (EOC) is the leading cause of gynecological-related cancer deaths in the United States. There is, therefore, an urgent need to develop novel therapeutic strategies for this devastating disease. Cellular senescence is a state of stable cell growth arrest that acts as an important tumor suppression mechanism. Ribonucleotide reductase M2 (RRM2) plays a key role in regulating the senescence-associated cell growth arrest by controlling biogenesis of 2'-deoxyribonucleoside 5'-triphosphates (dNTPs). The role of RRM2 in EOC remains poorly understood. Here we show that RRM2 is expressed at higher levels in EOCs compared with either normal ovarian surface epithelium (P<0.001) or fallopian tube epithelium (P<0.001). RRM2 expression significantly correlates with the expression of Ki67, a marker of cell proliferation (P<0.001). Moreover, RRM2 expression positively correlates with tumor grade and stage, and high RRM2 expression independently predicts a shorter overall survival in EOC patients (P<0.001). To delineate the functional role of RRM2 in EOC, we knocked down RRM2 expression in a panel of EOC cell lines. Knockdown of RRM2 expression inhibits the growth of human EOC cells. Mechanistically, RRM2 knockdown trig...Continue Reading


Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
Apr 28, 2004·The American Journal of Pathology·Ie-Ming Shih, Robert J Kurman
May 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Scott WadlerMario Sznol
Jun 8, 2006·Annual Review of Biochemistry·Pär Nordlund, Peter Reichard
Aug 22, 2006·Current Cancer Drug Targets·J ShaoYun Yen
Jan 24, 2007·Molecular and Cellular Biology·Rugang ZhangPeter D Adams
Jan 26, 2007·Nature·Andrea VenturaTyler Jacks
Aug 2, 2007·Nature Reviews. Molecular Cell Biology·Judith Campisi, Fabrizio d'Adda di Fagagna
Jan 15, 2008·Oncogene·S Courtois-CoxK Cichowski
Apr 23, 2008·Cell Research·John FarleyMichael J Birrer
Aug 14, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard W TothillDavid D L Bowtell
Oct 16, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Keren LevanonRonny Drapkin
Feb 4, 2010·Biochimica Et Biophysica Acta·Eiji FurutaKounosuke Watabe
Feb 16, 2010·The American Journal of Surgical Pathology·Robert J Kurman, Ie-Ming Shih
Aug 12, 2010·Nature Reviews. Clinical Oncology·Susana BanerjeeAlan Ashworth
Sep 23, 2010·Journal of the National Cancer Institute·Jonathan A EwaldDavid F Jarrard
Oct 12, 2010·Neoplasia : an International Journal for Oncology Research·Hayato FujitaMasao Tanaka
Nov 17, 2010·Genes & Development·Thomas KuilmanDaniel S Peeper
Jun 28, 2011·Nature Reviews. Cancer·Caterina NardellaPier Paolo Pandolfi
Jul 19, 2011·Developmental Cell·Daniel H Wainstock
Aug 6, 2011·Cancer Research·Benjamin G BitlerRugang Zhang
Sep 24, 2011·Nature Reviews. Cancer·Sebastian VaughanFrances R Balkwill
Oct 12, 2012·PloS One·Dylan T JonesKairbaan Hodivala-Dilke
Jan 22, 2013·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Mar 8, 2013·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Meng ZhangLiMing Wang


Feb 4, 2014·Cancer Letters·Katherine M Aird, Rugang Zhang
Apr 25, 2018·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Zehua WangCongjian Xu
Dec 10, 2015·Oncotarget·Paolo BenattiDiletta Dolfini
May 10, 2020·Molecular Oncology·Ying Z MazzuPhilip W Kantoff
Jul 1, 2014·Molecular & Cellular Oncology·Katherine M Aird, Rugang Zhang
Dec 20, 2017·International Journal of Molecular Sciences·Valentina SchmidtLuis A Martinez
Jul 15, 2017·Cellular and Molecular Life Sciences : CMLS·Corinne AbbadieAlbin Pourtier
May 4, 2018·Frontiers in Endocrinology·Raquel Buj, Katherine M Aird
Jun 15, 2016·Molecular Cancer Research : MCR·Nail FatkhutdinovRugang Zhang
May 22, 2019·Molecular Cancer Research : MCR·Erika S DahlKatherine M Aird
Aug 9, 2020·International Journal of Radiation Oncology, Biology, Physics·Qiuying TangSenxiang Yan

Related Concepts

Related Feeds

Barrett Esophagus

Barrett’s esophagus if a serious complication of gastroesophageal reflux disease during which the normal esophageal lining changes to tissue that resembles intestinal lining. Here is the latest research.