BIK drives an aggressive breast cancer phenotype through sublethal apoptosis and predicts poor prognosis of ER-positive breast cancer.

Cell Death & Disease
Vrajesh PandyaIng Swie Goping

Abstract

Apoptosis is fundamental to normal animal development and is the target for many anticancer therapies. Recent studies have explored the consequences of "failed apoptosis" where the apoptotic program is initiated but does not go to completion and does not cause cell death. Nevertheless, this failed apoptosis induces DNA double-strand breaks generating mutations that facilitate tumorigenesis. Whether failed apoptosis is relevant to clinical disease is unknown. BCL-2 interacting killer (BIK) is a stress-induced BH3-only protein that stimulates apoptosis in response to hormone and growth factor deprivation, hypoxia, and genomic stress. It was unclear whether BIK promotes or suppresses tumor survival within the context of breast cancer. We investigated this and show that BIK induces failed apoptosis with limited caspase activation and genomic damage in the absence of extensive cell death. Surviving cells acquire aggressive phenotypes characterized by enrichment of cancer stem-like cells, increased motility and increased clonogenic survival. Furthermore, by examining six independent cohorts of patients (total n = 969), we discovered that high BIK mRNA and protein levels predicted clinical relapse of Estrogen receptor (ER)-positive ca...Continue Reading

References

Mar 1, 1988·Experimental Cell Research·N P SinghE L Schneider
Jun 21, 1985·Science·Y TsujimotoC M Croce
Dec 31, 2002·Mutation Research·Krzysztof KońcaAndrzej Wojcik
Sep 4, 2003·Human Gene Therapy·Ulrike NaumannMichael Weller
Sep 27, 2003·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·M TomitaT Onitsuka
Nov 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kathryn R CoserToshi Shioda
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jingyung HurToshi Shioda
Feb 16, 2006·Journal of the National Cancer Institute·Christos SotiriouMauro Delorenzi
Mar 17, 2006·Breast Cancer Research and Treatment·Alessandro NeriEnrico Pinto
Jun 8, 2006·JAMA : the Journal of the American Medical Association·Lisa A CareyRobert C Millikan
Oct 10, 2006·FEBS Letters·Pedro J RealJose L Fernandez-Luna
Nov 21, 2007·The Journal of Cell Biology·Bernhard GillissenPeter T Daniel
Jun 11, 2008·Breast Cancer Research : BCR·Matthew J GrimshawJoy M Burchell
Jan 13, 2009·Cell Death and Differentiation·L C SpenderG J Inman
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kathryn R CoserToshi Shioda
Apr 7, 2010·Cell Stem Cell·Tanya Bondar, Ruslan Medzhitov
Jul 20, 2010·Oncogene·M M Lovric, C J Hawkins
Aug 4, 2010·Genes & Development·Verena LabiAndreas Villunger
Aug 11, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W Fraser SymmansLajos Pusztai
Oct 8, 2011·Breast Cancer Research : BCR·Achim RodyManfred Kaufmann
Mar 9, 2013·Cell Death and Differentiation·S BiswasS S Zinkel
Aug 27, 2013·Molecular Cancer Therapeutics·Christian Billard
Oct 1, 2013·The Breast : Official Journal of the European Society of Mastology·Philippe BertheauHugues de Thé
Jan 23, 2014·Cellular and Molecular Life Sciences : CMLS·Stéphanie Solier, Yves Pommier
Mar 1, 2014·British Journal of Cancer·Y LiuP J Coates

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Citations

Nov 13, 2020·The FEBS Journal·Camila Castillo FerrerGabriel Ichim
Jan 26, 2021·Cancer Biomarkers : Section a of Disease Markers·Magali EspinosaGisela Ceballos-Cancino
Jul 3, 2021·International Journal of Molecular Sciences·Christine J Hawkins, Mark A Miles

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Datasets Mentioned

BETA
GSE65194
GSE17705
GSE2990
42

Methods Mentioned

BETA
fluorescence-activated cell sorting
flow-cytometry
electrophoresis
FACS
exome sequencing
FCS
protein assay
X-ray
flow cytometry
transfections

Software Mentioned

ImageJ
BD
MATLAB
Flow Jo
GraphPad Prism
MedCalc
CaspLab
EPSON
ZEN2
MATLAB Bioinformatics Toolbox

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