STAT3 pathway regulates lung-derived brain metastasis initiating cell capacity through miR-21 activation

Oncotarget
Mohini SinghSheila K Singh

Abstract

Brain metastases (BM) represent the most common tumor to affect the adult central nervous system. Despite the increasing incidence of BM, likely due to consistently improving treatment of primary cancers, BM remain severely understudied. In this study, we utilized patient-derived stem cell lines from lung-to-brain metastases to examine the regulatory role of STAT3 in brain metastasis initiating cells (BMICs). Annotation of our previously described BMIC regulatory genes with protein-protein interaction network mapping identified STAT3 as a novel protein interactor. STAT3 knockdown showed a reduction in BMIC self-renewal and migration, and decreased tumor size in vivo. Screening of BMIC lines with a library of STAT3 inhibitors identified one inhibitor to significantly reduce tumor formation. Meta-analysis identified the oncomir microRNA-21 (miR-21) as a target of STAT3 activity. Inhibition of miR-21 displayed similar reductions in BMIC self-renewal and migration as STAT3 knockdown. Knockdown of STAT3 also reduced expression of known downstream targets of miR-21. Our studies have thus identified STAT3 and miR-21 as cooperative regulators of stemness, migration and tumor initiation in lung-derived BM. Therefore, STAT3 represents a ...Continue Reading

References

Sep 12, 1997·Science·J E Darnell
Oct 17, 2002·Journal of Neurology·Riccardo SoffiettiRoberto Mutani
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Jan 28, 2004·Human Pathology·Philip Th WentStephan Dirnhofer
Jun 4, 2004·Nature Biotechnology·Zhijin Wu, Rafael A Irizarry
Nov 19, 2004·Nature·Sheila K SinghPeter B Dirks
Jan 20, 2005·Bioinformatics·Kevin R Brown, Igor Jurisica
Feb 22, 2005·PLoS Biology·Julius BrenneckeStephen M Cohen
Mar 1, 2005·Journal of Clinical Pathology·N NathooS A Toms
Mar 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hui SongJiayuh Lin
Oct 4, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·David R HodgeWilliam L Farrar
Dec 3, 2005·Cancer Research·Anne T CollinsNorman J Maitland
Oct 25, 2006·Nature Reviews. Cancer·George A Calin, Carlo M Croce
Dec 23, 2006·Nature Reviews. Immunology·Hua YuDrew Pardoll
Apr 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Khandaker SiddiqueeJames Turkson
Aug 4, 2007·The Oncologist·April F Eichler, Jay S Loeffler
Nov 6, 2007·Trends in Molecular Medicine·Mahmut YilmazFrançois Lehembre
Dec 7, 2007·The Journal of Clinical Investigation·Sizhi Paul GaoJacqueline F Bromberg
Feb 14, 2008·Cell Research·Shuomin ZhuYin-Yuan Mo
Aug 21, 2008·Bioinformatics·Guangyong ZhengYixue Li
Oct 31, 2008·Nucleic Acids Research·Elodie Portales-CasamarWyeth W Wasserman
Nov 1, 2008·International Journal of Cancer. Journal International Du Cancer·Elisabetta FerrettiAlberto Gulino
May 26, 2009·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Virginia TirinoGiuseppe Pirozzi
Jul 16, 2009·Current Molecular Medicine·Eswaran Devarajan, Suyun Huang
Oct 20, 2009·Bioinformatics·Kevin R BrownIgor Jurisica
Jan 11, 2011·Bioorganic & Medicinal Chemistry·Vijay M ShahaniPatrick T Gunning
Feb 15, 2011·Oncogene·K SchramedeiK Brocke-Heidrich
May 28, 2011·ChemMedChem·Steven FletcherPatrick T Gunning
Jul 27, 2011·Bioorganic & Medicinal Chemistry Letters·Brent D G PagePatrick T Gunning
Sep 24, 2011·The Journal of Biological Chemistry·Chuan He YangLawrence M Pfeffer
Jan 17, 2012·Bioinformatics·Raivo KoldeJaak Vilo

❮ Previous
Next ❯

Citations

Mar 1, 2019·Cancers·Shang-Gin WuJin-Yuan Shih
Apr 23, 2020·International Journal of Molecular Sciences·Ruben Mercado SantosWen Cai Zhang
Jul 13, 2017·Tissue Engineering. Part a·Anthony MonteforteAaron B Baker
Nov 23, 2016·Cancer Metastasis Reviews·Chenyu Zhang, Dihua Yu
Jul 6, 2019·Frontiers in Genetics·Adenilson PereiraÂndrea Ribeiro-Dos-Santos
Jun 6, 2018·Frontiers in Oncology·Rute M S M PedrosaJohan M Kros
Oct 8, 2020·International Journal of Molecular Sciences·Chun-Chia ChengChun-Chao Chang
Jun 13, 2018·Nature Medicine·Neibla PriegoManuel Valiente
Feb 23, 2020·Molecular Cancer Research : MCR·Anchit KhannaJohn E Pimanda
Jul 1, 2021·Cell & Bioscience·Mei ZhangXin-Hua Liang
Jul 3, 2021·Pharmaceuticals·Sara VerduraJavier A Menendez

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
xenograft
xenografts
PCR
Fluorescence

Software Mentioned

FpClass
ImageScope
Bioconductor
NAViGaTOR
gcrma ( GeneChip Robust Multiarray Averaging
I2D
PAZAR
Graphpad Prism
RobustRankAggreg
miRDip

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.