Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors

Oncotarget
Tomer MeirsonHava Gil-Henn

Abstract

Metastatic dissemination of cancer cells from the primary tumor and their spread to distant sites in the body is the leading cause of mortality in breast cancer patients. While researchers have identified treatments that shrink or slow metastatic tumors, no treatment that permanently eradicates metastasis exists at present. Here, we show that the ABL kinase inhibitors imatinib, nilotinib, and GNF-5 impede invadopodium precursor formation and cortactin-phosphorylation dependent invadopodium maturation, leading to decreased actin polymerization in invadopodia, reduced extracellular matrix degradation, and impaired matrix proteolysis-dependent invasion. Using a mouse xenograft model we demonstrate that, while primary tumor size is not affected by ABL kinase inhibitors, the in vivo matrix metalloproteinase (MMP) activity, tumor cell invasion, and consequent spontaneous metastasis to lungs are significantly impaired in inhibitor-treated mice. Further proteogenomic analysis of breast cancer patient databases revealed co-expression of the Abl-related gene (Arg) and cortactin across all hormone- and human epidermal growth factor receptor 2 (HER2)-receptor status tumors, which correlates synergistically with distant metastasis and poor ...Continue Reading

References

May 1, 1996·Journal of Internal Medicine·J HallqvistC Reuterwall
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Aug 23, 2002·Leukemia Research·Anjali S Advani, Ann Marie Pendergast
Dec 20, 2002·Bioinformatics·Earl HubbellRui Mei
Apr 23, 2003·The Journal of Molecular Diagnostics : JMD·Chris CheadleKevin G Becker
May 31, 2003·Journal of Cell Science·Pamela J WoodringJean Y J Wang
Feb 5, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniela MateiMeei-Huey Jeng
Jul 17, 2004·Science·Neil P ShahCharles L Sawyers
Feb 3, 2005·The Journal of Cell Biology·Hideki YamaguchiJohn Condeelis
Feb 16, 2005·Cancer Cell·Ellen WeisbergJames D Griffin
Jun 16, 2006·The New England Journal of Medicine·Hagop KantarjianOliver G Ottmann
Jul 11, 2006·Clinical & Experimental Metastasis·Alissa M Weaver
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Rameen BeroukhimWilliam R Sellers
May 8, 2008·Current Biology : CB·Alissa M Weaver
May 13, 2008·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Stanley S StylliPeter Lock
Feb 5, 2009·Kidney International·Renée de MutsertFriedo W Dekker
Jan 15, 2010·Nature·Jianming ZhangNathanael S Gray
Apr 28, 2010·The Journal of Cell Biology·Marie SchoumacherDanijela M Vignjevic
Nov 27, 2010·Breast Cancer Research : BCR·Evanthia T RoussosJohn S Condeelis
Feb 10, 2011·Oncology Research·Mihoko SutohShigeru Tsuboi
Mar 15, 2011·Cancer Cell·Mark A EckertJing Yang
Mar 23, 2011·The Journal of Urology·Hayato YamamotoShigeru Tsuboi
Jul 5, 2011·Oncotarget·Mark A Eckert, Jing Yang
Nov 1, 2011·Nature Biotechnology·Mindy I DavisPatrick P Zarrinkar
Nov 23, 2011·The Journal of Cell Biology·Marco A O MagalhaesJohn Condeelis
Mar 6, 2012·Journal of Cell Science·Bojana GligorijevicJohn Condeelis
May 29, 2012·European Journal of Cell Biology·Hadas Sibony-Benyamini, Hava Gil-Henn
Apr 5, 2013·Molecular Biology of the Cell·Brian T BeatyJohn Condeelis
Jul 12, 2013·Nature Reviews. Cancer·Emileigh K GreuberAnn Marie Pendergast

❮ Previous
Next ❯

Citations

Oct 2, 2020·The Journal of Pathology. Clinical Research·Aiman AliMarco Magalhaes
Jul 12, 2018·F1000Research·Manoj Kumar Jena, Jagadeesh Janjanam
Nov 21, 2019·Oncogene·Tomer MeirsonAbraham O Samson
Aug 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hamad Ali HamadNur Fariesha Md Hashim
Mar 17, 2020·Cancer Biomarkers : Section a of Disease Markers·Xiaonan WangZhengsheng Wu
Jul 2, 2020·Molecular Cancer Therapeutics·Jill K Jones, Eric M Thompson
Nov 15, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Wenxia ZhaoRongguang Shao
Dec 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Miguel Angel Galván MoralesLuis M Teran
May 24, 2021·Cell Communication and Signaling : CCS·Jillian Hattaway LuttmanAnn Marie Pendergast
Aug 28, 2021·Cells·Trishna Saha, Hava Gil-Henn

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM6001
GSE5327
GSE45255

Methods Mentioned

BETA
xenograft

Software Mentioned

MAS
Leica LAS AF acquisition
ImageJ
IncuCyte
SPSS STATISTICA
MATLAB
cBioPortal
Seq V2 RSEM
Chemotaxis and Migration Tool
GraphPad

Related Concepts

Related Feeds

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Related Papers

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Tomer Meirson, Hava Gil-Henn
The Journal of Biological Chemistry
Pameeka S Smith-PearsonAnn Marie Pendergast
Methods in Molecular Biology
Ziqing WangGuangwei Du
© 2022 Meta ULC. All rights reserved