The pleiotropic effects of TNFα in breast cancer subtypes is regulated by TNFAIP3/A20

Oncogene
Eunmi LeeHasan Korkaya

Abstract

TNFα is a pleiotropic cytokine which fuels tumor cell growth, invasion, and metastasis in some malignancies, while in others it induces cytotoxic cell death. However, the molecular mechanism by which TNFα exerts its diverse effects on breast cancer subtypes remains elusive. Using in vitro assays and mouse xenografts, we show here that TNFα contributes to the aggressive properties of triple negative breast cancer (TNBC) cell lines via upregulation of TNFAIP3(A20). In a striking contrast, TNFα induces a potent cytotoxic cell death in luminal (ER+) breast cancer cell lines which fail to upregulate A20 expression. Overexpression of A20 not only protects luminal breast cancer cell lines from TNFα-induced cell death via inducing HSP70-mediated anti-apoptotic pathway but also promotes a robust EMT/CSC phenotype by activating the pStat3-mediated inflammatory signaling. Furthermore, A20 overexpression in luminal breast cancer cells induces aggressive metastatic properties in mouse xenografts via generating a permissive inflammatory microenvironment constituted by granulocytic-MDSCs. Collectively, our results reveal a mechanism by which A20 mediates pleiotropic effects of TNFα playing role in aggressive behaviors of TNBC subtype while it...Continue Reading

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Citations

May 12, 2020·Frontiers in Oncology·María Florencia MercoglianoRoxana Schillaci
Feb 8, 2020·Journal of Cellular Physiology·Hanwen LiXiawei Wei
Apr 15, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Fernanda WisnieskiMarilia Arruda Cardoso Smith
May 3, 2021·Cancer Letters·Yongyu ShiLining Zhang

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Methods Mentioned

BETA
flow cytometry
immunoprecipitation
pull-down
pulls
bioluminescence imaging
xenografts
bioluminescence
Transfection
reverse transcription–PCR
PCR

Software Mentioned

GraphPad Prism

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