TAK1 mediates microenvironment-triggered autocrine signals and promotes triple-negative breast cancer lung metastasis

Nature Communications
Oihana IriondoMin Yu

Abstract

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively. Compared to TAK1 inhibition, suppressing IL1 signaling with recombinant IL1 receptor antagonist (IL1RA) is less efficient in reducing lung metastasis, possibly due to the additional TAK1 signals coming from distinct stromal cells. Together, these observations suggest that TAK1 may play a central role in promoting TNBC cell adaptation to the lung microenvironment by facilitating positive feedback signaling mediated by P38. Approaches targeting the key TAK1-P38 signal could offer a novel means for suppressing TNBC lung metastasis.

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Citations

Sep 28, 2018·Journal of Cellular Biochemistry·Bagher FarhoodKeywan Mortezaee
Nov 1, 2018·Journal of Cellular Physiology·Masoud NajafiKeywan Mortezaee
Feb 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiali YinHaojun Luo
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Oct 1, 2020·Biological Research·Danxia CaoYongjun Liang
May 27, 2020·International Journal of Cancer. Journal International Du Cancer·Justin ZonnevilleAndrei V Bakin
Oct 23, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Seok Jong KangKyung Hoon Min
Nov 22, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elisa RodaPaola Rossi
Apr 2, 2021·Molecular and Cellular Biochemistry·Xian-Min LiTian-Lan Zhao
Apr 13, 2021·Journal of Biomedical Science·Sara Socorro FariaKelly Grace Magalhães
May 12, 2021·Angiogenesis·Linxin ZhuGuei-Sheung Liu

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Methods Mentioned

BETA
fluorescence-activated cell sorting
PCR
flow cytometry
FACS
xenograft
transfection
protein assay
flow

Software Mentioned

Oncomine

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