Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis

Nature Communications
Renxu ChangLixing Zhan

Abstract

Loss of WW domain-containing oxidoreductase (Wwox) expression has been observed in breast cancer (BC). However, its regulatory effects are largely unknown, especially in triple-negative breast cancer (TNBC). Herein, gene expression profiling revealed that JAK/STAT3 pathway was one of the most differentially modulated pathways in basal-like BC cells. The lower expression of Wwox was significantly correlated with high activation of STAT3 in basal-like cells and TNBC tissues. Overexpression of Wwox markedly inhibited proliferation and metastasis of BC cells by suppressing STAT3 activation, which is to interact with JAK2 to inhibit JAK2 and STAT3 phosphorylation. Furthermore, Wwox limited STAT3 binding to the interleukin-6 promoter, repressing expression of the IL-6 cytokine. Altogether, our data established that Wwox suppresses BC cell metastasis and proliferation by JAK2/STAT3 pathway. Targeting of Wwox with STAT3 could offer a promising therapeutic strategy for TNBC.

References

Aug 24, 1999·Cell·J F BrombergJ E Darnell
Aug 30, 2000·Nature·C M PerouD Botstein
Sep 13, 2001·Proceedings of the National Academy of Sciences of the United States of America·T SørlieA L Børresen-Dale
Jul 3, 2002·Nature Reviews. Immunology·Warren S Alexander
May 20, 2003·Nature Immunology·Ben A CrokerWarren S Alexander
May 20, 2003·Nature Immunology·Hideo YasukawaAkihiko Yoshimura
Dec 12, 2003·Nature Reviews. Immunology·Ke Shuai, Bin Liu
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Rami I AqeilanCarlo M Croce
May 8, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rami I AqeilanCarlo M Croce
Feb 5, 2005·Breast Cancer Research and Treatment·María I NunezC Marcelo Aldaz
Dec 20, 2005·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·E PłuciennikA K Bednarek
Nov 23, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce G HafftyDeborah Toppmeyer
Dec 5, 2006·Trends in Molecular Medicine·Nan-Shan ChangHamm-Ming Sheu
Dec 21, 2006·Cancer Research·Eugenio GaudioRami I Aqeilan
Jul 20, 2007·Cytokine·Michael FritzenwangerHans-R Figulla
Aug 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rebecca DentSteven A Narod
Oct 3, 2007·Cancer Research·Rami I AqeilanKlaus Elenius
Oct 5, 2007·Nature·Antoine E KarnoubRobert A Weinberg
Nov 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Peter M VoorheesRobert Z Orlowski
Apr 29, 2008·Nature Medicine·Greg FinakMorag Park
Feb 4, 2009·Breast Cancer Research : BCR·Xiao-Jun MaDennis C Sgroi
Aug 27, 2009·Journal of Cellular Biochemistry·Sara Del MareRami I Aqeilan
Dec 22, 2009·American Journal of Clinical Oncology·Anthony D Elias
Jun 3, 2011·The Journal of Clinical Investigation·Lauren L C MarottaKornelia Polyak
Jul 29, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jermaine CowardFrances R Balkwill
Oct 12, 2013·CA: a Cancer Journal for Clinicians·Carol DeSantisAhmedin Jemal

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Citations

Oct 24, 2018·Genes, Chromosomes & Cancer·Tabish HussainC Marcelo Aldaz
Dec 19, 2018·International Journal of Molecular Sciences·Sunny Trivedi, Michelle Starz-Gaiano
May 11, 2019·Cell Cycle·Suhaib K Abdeen, Rami I Aqeilan
Dec 10, 2019·The Journal of Experimental Medicine·Yirong WangYifeng Zhou
Aug 30, 2019·Cell Communication and Signaling : CCS·Shaojie JiangXiaoming Yang
Apr 18, 2020·Signal Transduction and Targeted Therapy·Saleh KhawaledRami I Aqeilan
May 16, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jiang-Jiang QinWei-Dong Zhang
Apr 22, 2020·International Ophthalmology·Nihan Bozkurt, Omer Ates
Apr 17, 2019·Cancer Research·Dipali Sharma
Jan 10, 2019·Cancer Research·Saleh KhawaledRami I Aqeilan
Nov 21, 2020·Neoplasia : an International Journal for Oncology Research·Zhihui ZhuHuajun Zhao
May 6, 2021·Cells·Karim TaouisFrançois Lallemand

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Datasets Mentioned

BETA
GSE110810

Methods Mentioned

BETA
RNA-seq
xenograft
immunoprecipitation
Co-immunoprecipitation
electrophoretic mobility shift assay
Antibody Array
enzyme-linked immunosorbent assay
ELISA
ubiquitination
PCR

Software Mentioned

Prism
KM plotter
ImageJ
tophat
Avadis NGS

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