The kinase Mirk/Dyrk1B mediates cell survival in pancreatic ductal adenocarcinoma

Cancer Research
Xiaobing DengEileen Friedman

Abstract

Ductal adenocarcinoma of the pancreas is almost uniformly lethal as this cancer is invariably detected at an advanced stage and is resistant to treatment. The serine/threonine kinase Mirk/Dyrk1B has been shown to be antiapoptotic in rhabdomyosarcomas. We have now investigated whether Mirk might mediate survival in another cancer in which Mirk is widely expressed, pancreatic ductal adenocarcinoma. Mirk was an active kinase in each pancreatic cancer cell line where it was detected. Mirk knockdown by RNA interference (RNAi) reduced the clonogenicity of Panc1 pancreatic cancer cells 4-fold and decreased tumor cell number, showing that Mirk mediates survival in these cells. Mirk knockdown by synthetic duplex RNAis in Panc1, AsPc1, and SU86.86 pancreatic cancer cells induced apoptosis and enhanced the apoptosis induced by gemcitibine. Mirk knockdown did not increase the abundance or activation of Akt. However, four of five pancreatic carcinoma cell lines exhibited either elevated Mirk activity or elevated Akt activity, suggesting that pancreatic cancer cells primarily rely on Mirk or Akt for survival signaling. Mirk protein was detected by immunohistochemistry in 25 of 28 cases (89%) of pancreatic ductal adenocarcinoma, with elevated...Continue Reading

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Citations

Oct 16, 2008·The Journal of Biological Chemistry·Olga BogachevaDon M Wojchowski
Jan 1, 2010·Carcinogenesis·Cao YangZhenfeng Duan
Feb 2, 2012·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Ahmed F YousefJoe S Mymryk
May 12, 2011·Sarcoma·Eileen Friedman
Sep 1, 2011·Molecular Cancer Therapeutics·Daina Z EwtonEileen A Friedman
Jan 26, 2013·PloS One·Bingyan WangRobert M Nissen
Jan 21, 2011·World Journal of Surgery·Guisheng ZhouF Charles Brunicardi
Mar 5, 2014·Carcinogenesis·Xiaobing DengEileen Friedman
Mar 17, 2010·Genes, Chromosomes & Cancer·Riina KuuseloAnne Kallioniemi
Dec 17, 2008·Developmental Cell·Ariadna LagunaMaria L Arbonés
Jul 7, 2015·Bioorganic & Medicinal Chemistry·So MasakiMasatoshi Hagiwara
Nov 24, 2017·International Journal of Molecular Sciences·Kenji Tanabe
Jun 23, 2007·Journal of Cellular Biochemistry·Eileen Friedman
Oct 30, 2014·Genes & Cancer·Xiaobing Deng, Eileen Friedman
Oct 15, 2018·Cellular and Molecular Life Sciences : CMLS·Rajeev SinghMatthias Lauth
Jan 29, 2021·World Journal of Stem Cells·Nikolaos Kokkorakis, Maria Gaitanou
Jun 19, 2021·Journal of Medicinal Chemistry·David Lee WalmsleyRoderick E Hubbard
Oct 29, 2021·Journal of Cellular and Molecular Medicine·Andrew J MasseyDavid Lee Walmsley

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