Cargando…
TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis
TGF‐β‐activated kinase 1 (TAK1), a serine/threonine kinase, is a key intermediate in several signaling pathways. However, its role in tumorigenesis is still not understood well. In this study, it is found that TAK1 expression decreases in esophageal tumor tissues and cell lines. In vitro experiments...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927628/ https://www.ncbi.nlm.nih.gov/pubmed/33717835 http://dx.doi.org/10.1002/advs.202001575 |
_version_ | 1783659716496326656 |
---|---|
author | Shi, Hui Ju, Qianqian Mao, Yinting Wang, Yuejun Ding, Jie Liu, Xiaoyu Tang, Xin Sun, Cheng |
author_facet | Shi, Hui Ju, Qianqian Mao, Yinting Wang, Yuejun Ding, Jie Liu, Xiaoyu Tang, Xin Sun, Cheng |
author_sort | Shi, Hui |
collection | PubMed |
description | TGF‐β‐activated kinase 1 (TAK1), a serine/threonine kinase, is a key intermediate in several signaling pathways. However, its role in tumorigenesis is still not understood well. In this study, it is found that TAK1 expression decreases in esophageal tumor tissues and cell lines. In vitro experiments demonstrate that proliferation of esophageal tumor cells is enhanced by knockdown of TAK1 expression and attenuated by elevated expression of TAK1. Using a subcutaneous tumor model, these observations are confirmed in vivo. Based on the results from co‐immunoprecipitation coupled with mass spectrometry, Ras association domain family 9 (RASSF9) is identified as a downstream target of TAK1. TAK1 phosphorylates RASSF9 at S284, which leads to reduced RAS dimerization, thereby blocking RAF/MEK/ERK signal transduction. Clinical survey reveals that TAK1 expression is inversely correlated with survival in esophageal cancer patients. Taken together, the data reveal that TAK1‐mediated phosphorylation of RASSF9 at Ser284 negatively regulates esophageal tumor cell proliferation via inhibition of the RAS/MEK/ERK axis. |
format | Online Article Text |
id | pubmed-7927628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79276282021-03-12 TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis Shi, Hui Ju, Qianqian Mao, Yinting Wang, Yuejun Ding, Jie Liu, Xiaoyu Tang, Xin Sun, Cheng Adv Sci (Weinh) Full Papers TGF‐β‐activated kinase 1 (TAK1), a serine/threonine kinase, is a key intermediate in several signaling pathways. However, its role in tumorigenesis is still not understood well. In this study, it is found that TAK1 expression decreases in esophageal tumor tissues and cell lines. In vitro experiments demonstrate that proliferation of esophageal tumor cells is enhanced by knockdown of TAK1 expression and attenuated by elevated expression of TAK1. Using a subcutaneous tumor model, these observations are confirmed in vivo. Based on the results from co‐immunoprecipitation coupled with mass spectrometry, Ras association domain family 9 (RASSF9) is identified as a downstream target of TAK1. TAK1 phosphorylates RASSF9 at S284, which leads to reduced RAS dimerization, thereby blocking RAF/MEK/ERK signal transduction. Clinical survey reveals that TAK1 expression is inversely correlated with survival in esophageal cancer patients. Taken together, the data reveal that TAK1‐mediated phosphorylation of RASSF9 at Ser284 negatively regulates esophageal tumor cell proliferation via inhibition of the RAS/MEK/ERK axis. John Wiley and Sons Inc. 2021-01-06 /pmc/articles/PMC7927628/ /pubmed/33717835 http://dx.doi.org/10.1002/advs.202001575 Text en © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers Shi, Hui Ju, Qianqian Mao, Yinting Wang, Yuejun Ding, Jie Liu, Xiaoyu Tang, Xin Sun, Cheng TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis |
title | TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis |
title_full | TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis |
title_fullStr | TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis |
title_full_unstemmed | TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis |
title_short | TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis |
title_sort | tak1 phosphorylates rassf9 and inhibits esophageal squamous tumor cell proliferation by targeting the ras/mek/erk axis |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927628/ https://www.ncbi.nlm.nih.gov/pubmed/33717835 http://dx.doi.org/10.1002/advs.202001575 |
work_keys_str_mv | AT shihui tak1phosphorylatesrassf9andinhibitsesophagealsquamoustumorcellproliferationbytargetingtherasmekerkaxis AT juqianqian tak1phosphorylatesrassf9andinhibitsesophagealsquamoustumorcellproliferationbytargetingtherasmekerkaxis AT maoyinting tak1phosphorylatesrassf9andinhibitsesophagealsquamoustumorcellproliferationbytargetingtherasmekerkaxis AT wangyuejun tak1phosphorylatesrassf9andinhibitsesophagealsquamoustumorcellproliferationbytargetingtherasmekerkaxis AT dingjie tak1phosphorylatesrassf9andinhibitsesophagealsquamoustumorcellproliferationbytargetingtherasmekerkaxis AT liuxiaoyu tak1phosphorylatesrassf9andinhibitsesophagealsquamoustumorcellproliferationbytargetingtherasmekerkaxis AT tangxin tak1phosphorylatesrassf9andinhibitsesophagealsquamoustumorcellproliferationbytargetingtherasmekerkaxis AT suncheng tak1phosphorylatesrassf9andinhibitsesophagealsquamoustumorcellproliferationbytargetingtherasmekerkaxis |