Urokinase signaling through its receptor protects against anoikis by increasing BCL-xL expression levels

The Journal of Biological Chemistry
Daniela AlfanoM Patrizia Stoppelli

Abstract

The acquired capabilities of resistance to apoptotic cell death and tissue invasion are considered to be obligate steps in tumor progression. The binding of the serine protease urokinase (uPA) to its receptor (uPAR) plays a central role in the molecular events coordinating tumor cell adhesion, migration, and invasion. Here we investigate whether uPAR signaling may also prevent apoptosis following loss of anchorage (anoikis) or DNA damage. If nontransformed human retinal pigment epithelial cells are pre-exposed to uPA or to its noncatalytic amino-terminal region (residues 1-135), they exhibit a markedly reduced susceptibility to anoikis as well as to UV-induced apoptosis. This anti-apoptotic effect is retained by a uPA-derived synthetic peptide corresponding to the receptor binding domain and is inhibited by anti-uPAR polyclonal antibodies. Furthermore, the stable reduction of uPA or uPAR expression by RNA interference leads to an increased susceptibility to UV-, cisplatin-, and detachment-induced apoptosis. In particular, the level of uPAR expression positively correlates with cell resistance to anoikis. The protective ability of uPA is prevented by UO126, LY294002, by an MAPK targeting small interference RNA, and by a dominant...Continue Reading

References

Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J C KirchheimerB R Binder
Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·M P StoppelliR K Assoian
Feb 1, 1994·The Journal of Cell Biology·S M Frisch, H Francis
Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Sep 9, 2000·Current Opinion in Cell Biology·L Ossowski, J A Aguirre-Ghiso
Sep 9, 2000·Current Opinion in Cell Biology·K T PreissnerA E May
Apr 24, 2001·Genes & Development·A SchulzeJ Downward
Jun 5, 2001·Apoptosis : an International Journal on Programmed Cell Death·A Danilkovitch-Miagkova, E J Leonard
Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·M ResnatiF Blasi
Jun 28, 2002·Cancer Cell·Douglas R Green, Gerard I Evan
Sep 26, 2002·The Journal of Biological Chemistry·Nunzia MontuoriPia Ragno
Oct 3, 2002·Nature Reviews. Cancer·Stella PelengarisGerard Evan
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·Francesco Blasi, Peter Carmeliet
Mar 15, 2003·Nature Reviews. Cancer·John D Hood, David A Cheresh
May 10, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Olivier MeilhacEduardo Anglés-Cano
Jul 23, 2003·Current Pharmaceutical Design·Matthias C KuglerHarold A Chapman
Nov 20, 2003·The Journal of Biological Chemistry·Xue WangAugustine M K Choi
Dec 31, 2003·The Journal of Biological Chemistry·Patrick RossignolEduardo Anglés-Cano
Apr 20, 2004·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xingyao BuWalter E Laug
Feb 16, 2005·Thrombosis and Haemostasis·Daniela AlfanoMaria Patrizia Stoppelli
Apr 21, 2005·Thrombosis and Haemostasis·Keld DanøJohn Rømer
May 4, 2005·The Journal of Biological Chemistry·Lucia GargiuloMaria V Carriero

❮ Previous
Next ❯

Citations

Apr 17, 2013·Apoptosis : an International Journal on Programmed Cell Death·Sun Hee ParkSteven M Frisch
Jul 26, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Manuel A PalleroJoanne E Murphy-Ullrich
Nov 1, 2006·Anti-cancer Drugs·Shinichi NozakiEtsuhide Yamamoto
Jul 16, 2010·The Journal of Clinical Investigation·Aditya MurthyRama Khokha
Aug 25, 2006·Cancer Cell International·Inder SehgalJoseph Francis
Oct 22, 2010·RNA·Daniel Miotto DupontPeter André Andreasen
Mar 1, 2007·PloS One·Margarita GutovaKaren S Aboody
Aug 6, 2013·Journal of Cancer Research and Clinical Oncology·Kevin TanJia-Lin Yang
Aug 1, 2007·The Journal of Cell Biology·Robin D LesterSteven L Gonias
Jan 23, 2016·Cancer Letters·Lauren MacDonaghMartin P Barr
Mar 2, 2016·Bioconjugate Chemistry·Daniel M DupontJan K Jensen
Apr 25, 2009·International Journal of Cancer. Journal International Du Cancer·Hao ZhouChunxu Zhang
Aug 19, 2015·Frontiers in Pharmacology·Steven L Gonias, Jingjing Hu
Jan 31, 2012·Medical Hypotheses·Janaina FernandesClaudia de Alencar S Lage
Nov 23, 2006·The International Journal of Biochemistry & Cell Biology·Massimo P Crippa
Jan 25, 2017·Frontiers of Medicine·Melvin E Klegerman
Dec 1, 2017·Cellular and Molecular Life Sciences : CMLS·Gabriele EdenBernard Degryse
Nov 3, 2017·Apoptosis : an International Journal on Programmed Cell Death·Kai-Xuan SunZhi-Hong Zong
Aug 15, 2018·Journal of Cellular Physiology·Hojjat Naderi-Meshkin, Naghmeh Ahmadiankia
Oct 23, 2010·Expert Review of Molecular Diagnostics·Karin MengeleManfred Schmitt
Mar 23, 2013·Chembiochem : a European Journal of Chemical Biology·Paola FrancoMaria Patrizia Stoppelli
Apr 10, 2019·Cancers·Chiara AgnolettoStefano Volinia
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Kathleen K M GloverKevin M Coombs
Dec 1, 2013·Oncology Letters·Diandra D RandleValerie A Odero-Marah
Feb 5, 2021·Journal of Clinical Medicine·Filomena Napolitano, Nunzia Montuori
Jan 14, 2021·International Journal of Molecular Sciences·Han Yeoung LeeJong Kook Park
Mar 1, 2012·Journal of Cell Science·Daniela AlfanoAnne J Ridley

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

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

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.