Cargando…
STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling
Yes‐associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778644/ https://www.ncbi.nlm.nih.gov/pubmed/31393050 http://dx.doi.org/10.1111/cas.14166 |
_version_ | 1783456799131697152 |
---|---|
author | Tang, Dong‐E Dai, Yong Lin, Lie‐Wen Xu, Yong Liu, Dong‐Zhou Hong, Xiao‐Ping Jiang, Hao‐Wu Xu, Song‐Hui |
author_facet | Tang, Dong‐E Dai, Yong Lin, Lie‐Wen Xu, Yong Liu, Dong‐Zhou Hong, Xiao‐Ping Jiang, Hao‐Wu Xu, Song‐Hui |
author_sort | Tang, Dong‐E |
collection | PubMed |
description | Yes‐associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in different types of human cancers. However, the molecular mechanism of YAP1 upregulation in cancer is still unclear. Here we report that the E3 ubiquitin ligase STUB1 ubiquitinates and destabilizes YAP1, thereby inhibiting cancer cell survival. Low levels of STUB1 expression were correlated with increased protein levels of YAP1 in human gastric cancer cell lines and patient samples. Moreover, we revealed that STUB1 ubiquitinates YAP1 at the K280 site by K48‐linked polyubiquitination, which in turn increases YAP1 turnover and promotes cellular chemosensitivity. Overall, our study establishes YAP1 ubiquitination and degradation mediated by the E3 ligase STUB1 as an important regulatory mechanism in gastric cancer, and provides a rationale for potential therapeutic interventions. |
format | Online Article Text |
id | pubmed-6778644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67786442019-10-11 STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling Tang, Dong‐E Dai, Yong Lin, Lie‐Wen Xu, Yong Liu, Dong‐Zhou Hong, Xiao‐Ping Jiang, Hao‐Wu Xu, Song‐Hui Cancer Sci Original Articles Yes‐associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in different types of human cancers. However, the molecular mechanism of YAP1 upregulation in cancer is still unclear. Here we report that the E3 ubiquitin ligase STUB1 ubiquitinates and destabilizes YAP1, thereby inhibiting cancer cell survival. Low levels of STUB1 expression were correlated with increased protein levels of YAP1 in human gastric cancer cell lines and patient samples. Moreover, we revealed that STUB1 ubiquitinates YAP1 at the K280 site by K48‐linked polyubiquitination, which in turn increases YAP1 turnover and promotes cellular chemosensitivity. Overall, our study establishes YAP1 ubiquitination and degradation mediated by the E3 ligase STUB1 as an important regulatory mechanism in gastric cancer, and provides a rationale for potential therapeutic interventions. John Wiley and Sons Inc. 2019-08-28 2019-10 /pmc/articles/PMC6778644/ /pubmed/31393050 http://dx.doi.org/10.1111/cas.14166 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Tang, Dong‐E Dai, Yong Lin, Lie‐Wen Xu, Yong Liu, Dong‐Zhou Hong, Xiao‐Ping Jiang, Hao‐Wu Xu, Song‐Hui STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling |
title | STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling |
title_full | STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling |
title_fullStr | STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling |
title_full_unstemmed | STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling |
title_short | STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling |
title_sort | stub1 suppresseses tumorigenesis and chemoresistance through antagonizing yap1 signaling |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778644/ https://www.ncbi.nlm.nih.gov/pubmed/31393050 http://dx.doi.org/10.1111/cas.14166 |
work_keys_str_mv | AT tangdonge stub1suppressesestumorigenesisandchemoresistancethroughantagonizingyap1signaling AT daiyong stub1suppressesestumorigenesisandchemoresistancethroughantagonizingyap1signaling AT linliewen stub1suppressesestumorigenesisandchemoresistancethroughantagonizingyap1signaling AT xuyong stub1suppressesestumorigenesisandchemoresistancethroughantagonizingyap1signaling AT liudongzhou stub1suppressesestumorigenesisandchemoresistancethroughantagonizingyap1signaling AT hongxiaoping stub1suppressesestumorigenesisandchemoresistancethroughantagonizingyap1signaling AT jianghaowu stub1suppressesestumorigenesisandchemoresistancethroughantagonizingyap1signaling AT xusonghui stub1suppressesestumorigenesisandchemoresistancethroughantagonizingyap1signaling |