TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis

F-actin dynamics is crucial for many fundamental properties of cancer cells, from cell-substrate adhesion to migration, invasion and metastasis. However, the regulatory mechanisms of actin dynamics are still incompletely understood. In this study, we demonstrate the function of a protein named TM9SF...

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Autores principales: Meng, Zhaoyue, Li, Zhichao, Xie, Mingxu, Yu, Hongyan, Jiang, Liwen, Yao, Xiaoqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522921/
https://www.ncbi.nlm.nih.gov/pubmed/36175399
http://dx.doi.org/10.1038/s41467-022-33276-y
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author Meng, Zhaoyue
Li, Zhichao
Xie, Mingxu
Yu, Hongyan
Jiang, Liwen
Yao, Xiaoqiang
author_facet Meng, Zhaoyue
Li, Zhichao
Xie, Mingxu
Yu, Hongyan
Jiang, Liwen
Yao, Xiaoqiang
author_sort Meng, Zhaoyue
collection PubMed
description F-actin dynamics is crucial for many fundamental properties of cancer cells, from cell-substrate adhesion to migration, invasion and metastasis. However, the regulatory mechanisms of actin dynamics are still incompletely understood. In this study, we demonstrate the function of a protein named TM9SF4 in regulating actin dynamics and controlling cancer cell motility and metastasis. We show that an N-terminal fragment (NTF) cleaved from TM9SF4 can directly bind to F-actin to induce actin oxidation at Cys374, consequently enhancing cofilin-mediated F-actin disassembly. Knockdown of TM9SF4 reduces cell migration and invasion in ovarian cancer cells A2780, SKOV3 and several high grade serous ovarian cancer lines (HGSOCs). In vivo, knockdown of TM9SF4 completely abolishes the tumor growth and metastasis in athymic nude mice. These data provide mechanistic insights into TM9SF4-mediated regulation of actin dynamics in ovarian cancer cells.
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spelling pubmed-95229212022-10-01 TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis Meng, Zhaoyue Li, Zhichao Xie, Mingxu Yu, Hongyan Jiang, Liwen Yao, Xiaoqiang Nat Commun Article F-actin dynamics is crucial for many fundamental properties of cancer cells, from cell-substrate adhesion to migration, invasion and metastasis. However, the regulatory mechanisms of actin dynamics are still incompletely understood. In this study, we demonstrate the function of a protein named TM9SF4 in regulating actin dynamics and controlling cancer cell motility and metastasis. We show that an N-terminal fragment (NTF) cleaved from TM9SF4 can directly bind to F-actin to induce actin oxidation at Cys374, consequently enhancing cofilin-mediated F-actin disassembly. Knockdown of TM9SF4 reduces cell migration and invasion in ovarian cancer cells A2780, SKOV3 and several high grade serous ovarian cancer lines (HGSOCs). In vivo, knockdown of TM9SF4 completely abolishes the tumor growth and metastasis in athymic nude mice. These data provide mechanistic insights into TM9SF4-mediated regulation of actin dynamics in ovarian cancer cells. Nature Publishing Group UK 2022-09-29 /pmc/articles/PMC9522921/ /pubmed/36175399 http://dx.doi.org/10.1038/s41467-022-33276-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Meng, Zhaoyue
Li, Zhichao
Xie, Mingxu
Yu, Hongyan
Jiang, Liwen
Yao, Xiaoqiang
TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis
title TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis
title_full TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis
title_fullStr TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis
title_full_unstemmed TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis
title_short TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis
title_sort tm9sf4 is an f-actin disassembly factor that promotes tumor progression and metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522921/
https://www.ncbi.nlm.nih.gov/pubmed/36175399
http://dx.doi.org/10.1038/s41467-022-33276-y
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