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AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α

TNF-α plays a crucial role in cancer initiation and progression by enhancing cancer cell proliferation, survival, and migration. Even though the known functional role of AWP1 (zinc finger AN1 type-6, ZFAND6) is as a key mediator of TNF-α signaling, its potential role in the TNF-α-dependent responses...

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Autores principales: Kim, Eun-Young, Kim, Ji-Eun, Choi, Bongkun, Kweon, Jiyeon, Park, Si-On, Lee, Hee-Seop, Lee, Eun-Jin, Oh, Soyoon, Shin, Ha Rim, Choi, Hyuksu, Kim, Yongsub, Chang, Eun-Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012775/
https://www.ncbi.nlm.nih.gov/pubmed/33816268
http://dx.doi.org/10.3389/fonc.2021.631469
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author Kim, Eun-Young
Kim, Ji-Eun
Choi, Bongkun
Kweon, Jiyeon
Park, Si-On
Lee, Hee-Seop
Lee, Eun-Jin
Oh, Soyoon
Shin, Ha Rim
Choi, Hyuksu
Kim, Yongsub
Chang, Eun-Ju
author_facet Kim, Eun-Young
Kim, Ji-Eun
Choi, Bongkun
Kweon, Jiyeon
Park, Si-On
Lee, Hee-Seop
Lee, Eun-Jin
Oh, Soyoon
Shin, Ha Rim
Choi, Hyuksu
Kim, Yongsub
Chang, Eun-Ju
author_sort Kim, Eun-Young
collection PubMed
description TNF-α plays a crucial role in cancer initiation and progression by enhancing cancer cell proliferation, survival, and migration. Even though the known functional role of AWP1 (zinc finger AN1 type-6, ZFAND6) is as a key mediator of TNF-α signaling, its potential role in the TNF-α-dependent responses of cancer cells remains unclear. In our current study, we found that an AWP1 knockdown using short hairpin RNAs increases the migratory potential of non-aggressive MCF-7 breast cancer cells with no significant alteration of their proliferation in response to TNF-α. A CRISPR/Cas9-mediated AWP1 knockout in MCF-7 cells led to mesenchymal cell type morphological changes and an accelerated motility. TNF-α administration further increased this migratory capacity of these AWP1-depleted cells through the activation of NF-κB accompanied by increased epithelial-mesenchymal transition-related gene expression. In particular, an AWP1 depletion augmented the expression of Nox1, reactive oxygen species (ROS) generating enzymes, and ROS levels and subsequently promoted the migratory potential of MCF-7 cells mediated by TNF-α. These TNF-α-mediated increases in the chemotactic migration of AWP1 knockout cells were completely abrogated by an NF-κB inhibitor and a ROS scavenger. Our results suggest that a loss-of-function of AWP1 alters the TNF-α response of non-aggressive breast cancer cells by potentiating ROS-dependent NF-κB activation.
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spelling pubmed-80127752021-04-02 AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α Kim, Eun-Young Kim, Ji-Eun Choi, Bongkun Kweon, Jiyeon Park, Si-On Lee, Hee-Seop Lee, Eun-Jin Oh, Soyoon Shin, Ha Rim Choi, Hyuksu Kim, Yongsub Chang, Eun-Ju Front Oncol Oncology TNF-α plays a crucial role in cancer initiation and progression by enhancing cancer cell proliferation, survival, and migration. Even though the known functional role of AWP1 (zinc finger AN1 type-6, ZFAND6) is as a key mediator of TNF-α signaling, its potential role in the TNF-α-dependent responses of cancer cells remains unclear. In our current study, we found that an AWP1 knockdown using short hairpin RNAs increases the migratory potential of non-aggressive MCF-7 breast cancer cells with no significant alteration of their proliferation in response to TNF-α. A CRISPR/Cas9-mediated AWP1 knockout in MCF-7 cells led to mesenchymal cell type morphological changes and an accelerated motility. TNF-α administration further increased this migratory capacity of these AWP1-depleted cells through the activation of NF-κB accompanied by increased epithelial-mesenchymal transition-related gene expression. In particular, an AWP1 depletion augmented the expression of Nox1, reactive oxygen species (ROS) generating enzymes, and ROS levels and subsequently promoted the migratory potential of MCF-7 cells mediated by TNF-α. These TNF-α-mediated increases in the chemotactic migration of AWP1 knockout cells were completely abrogated by an NF-κB inhibitor and a ROS scavenger. Our results suggest that a loss-of-function of AWP1 alters the TNF-α response of non-aggressive breast cancer cells by potentiating ROS-dependent NF-κB activation. Frontiers Media S.A. 2021-03-18 /pmc/articles/PMC8012775/ /pubmed/33816268 http://dx.doi.org/10.3389/fonc.2021.631469 Text en Copyright © 2021 Kim, Kim, Choi, Kweon, Park, Lee, Lee, Oh, Shin, Choi, Kim and Chang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Kim, Eun-Young
Kim, Ji-Eun
Choi, Bongkun
Kweon, Jiyeon
Park, Si-On
Lee, Hee-Seop
Lee, Eun-Jin
Oh, Soyoon
Shin, Ha Rim
Choi, Hyuksu
Kim, Yongsub
Chang, Eun-Ju
AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α
title AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α
title_full AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α
title_fullStr AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α
title_full_unstemmed AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α
title_short AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α
title_sort awp1 restrains the aggressive behavior of breast cancer cells induced by tnf-α
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012775/
https://www.ncbi.nlm.nih.gov/pubmed/33816268
http://dx.doi.org/10.3389/fonc.2021.631469
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