AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-alpha
- Abstract
- TNF-alpha 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-alpha signaling, its potential role in the TNF-alpha-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-alpha. A CRISPR/Cas9-mediated AWP1 knockout in MCF-7 cells led to mesenchymal cell type morphological changes and an accelerated motility. TNF-alpha administration further increased this migratory capacity of these AWP1-depleted cells through the activation of NF-kappa B 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-alpha. These TNF-alpha-mediated increases in the chemotactic migration of AWP1 knockout cells were completely abrogated by an NF-kappa B inhibitor and a ROS scavenger. Our results suggest that a loss-of-function of AWP1 alters the TNF-alpha response of non-aggressive breast cancer cells by potentiating ROS-dependent NF-kappa B activation.
- Author(s)
- 김은영; 김지은; 최봉근; 권지연; 박시온; 이희섭; 이은진; 오소윤; 신하림; 최혁수; 김용섭; 장은주
- Issued Date
- 2021
- Type
- Article
- Keyword
- AWP1; breast cancer; epithelial–mesenchymal transition; migration; NF-κB; Oncology; reactive oxygen species; TNF-α
- DOI
- 10.3389/fonc.2021.631469
- URI
- https://oak.ulsan.ac.kr/handle/2021.oak/7306
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_244a86a65ec14995a730ec74a0c47b4f&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,AWP1%20Restrains%20the%20Aggressive%20Behavior%20of%20Breast%20Cancer%20Cells%20Induced%20by%20TNF-alpha&sortby=rank&pcAvailability=true
- Publisher
- FRONTIERS IN ONCOLOGY
- Location
- 스위스
- Language
- 영어
- ISSN
- 2234-943X
- Citation Volume
- 11
- Citation Number
- 0
- Citation Start Page
- 0
- Citation End Page
- 0
-
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- Medicine > Medicine
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