Cargando…
WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression
WW domain binding protein-2 (WBP2) can function as a Yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) co-activator and has a crucial role in promoting breast cancer progression. However, the expression and potential molecular mechanisms of WBP2 in the context of l...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035140/ https://www.ncbi.nlm.nih.gov/pubmed/33837178 http://dx.doi.org/10.1038/s41419-021-03600-3 |
_version_ | 1783676664831541248 |
---|---|
author | Han, Qiang Rong, Xuezhu Lin, Xuyong Zhang, Xiupeng Fan, Chuifeng Zhao, Huanyu Wang, Enhua |
author_facet | Han, Qiang Rong, Xuezhu Lin, Xuyong Zhang, Xiupeng Fan, Chuifeng Zhao, Huanyu Wang, Enhua |
author_sort | Han, Qiang |
collection | PubMed |
description | WW domain binding protein-2 (WBP2) can function as a Yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) co-activator and has a crucial role in promoting breast cancer progression. However, the expression and potential molecular mechanisms of WBP2 in the context of lung cancer are not fully understood. We determined that WBP2 was highly expressed in lung cancer specimens and cell lines and that this expression was closely related to the advanced pTNM stage, lymph node metastasis, and poor prognosis of patients. In addition, gain- and loss-of-function experiments revealed that WBP2 could significantly promote the proliferation and invasion of lung cancer cells both in vivo and in vitro. To elucidate the underlying molecular mechanism, we determined that wild-type WBP2 could competitively bind to the WW domain of WWC3 (WW and C2 domain-containing-3) with LATS1 (Large tumor suppressor-1) through its PPxY motifs, thus inhibiting the formation of the WWC3-LATS1 complex, reducing the phosphorylation level of LATS1, suppressing the activity of the Hippo pathway, and ultimately promoting YAP nuclear translocation. Therefore, from the aspect of upstream molecules of Hippo signaling, WBP2 promotes the malignant phenotype of lung cancer cells in a unique manner that is not directly dependent upon YAP, thus providing a corresponding experimental basis for the development of targeted therapeutic drugs for lung cancer. |
format | Online Article Text |
id | pubmed-8035140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80351402021-04-27 WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression Han, Qiang Rong, Xuezhu Lin, Xuyong Zhang, Xiupeng Fan, Chuifeng Zhao, Huanyu Wang, Enhua Cell Death Dis Article WW domain binding protein-2 (WBP2) can function as a Yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) co-activator and has a crucial role in promoting breast cancer progression. However, the expression and potential molecular mechanisms of WBP2 in the context of lung cancer are not fully understood. We determined that WBP2 was highly expressed in lung cancer specimens and cell lines and that this expression was closely related to the advanced pTNM stage, lymph node metastasis, and poor prognosis of patients. In addition, gain- and loss-of-function experiments revealed that WBP2 could significantly promote the proliferation and invasion of lung cancer cells both in vivo and in vitro. To elucidate the underlying molecular mechanism, we determined that wild-type WBP2 could competitively bind to the WW domain of WWC3 (WW and C2 domain-containing-3) with LATS1 (Large tumor suppressor-1) through its PPxY motifs, thus inhibiting the formation of the WWC3-LATS1 complex, reducing the phosphorylation level of LATS1, suppressing the activity of the Hippo pathway, and ultimately promoting YAP nuclear translocation. Therefore, from the aspect of upstream molecules of Hippo signaling, WBP2 promotes the malignant phenotype of lung cancer cells in a unique manner that is not directly dependent upon YAP, thus providing a corresponding experimental basis for the development of targeted therapeutic drugs for lung cancer. Nature Publishing Group UK 2021-04-09 /pmc/articles/PMC8035140/ /pubmed/33837178 http://dx.doi.org/10.1038/s41419-021-03600-3 Text en © The Author(s) 2021 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 Han, Qiang Rong, Xuezhu Lin, Xuyong Zhang, Xiupeng Fan, Chuifeng Zhao, Huanyu Wang, Enhua WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression |
title | WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression |
title_full | WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression |
title_fullStr | WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression |
title_full_unstemmed | WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression |
title_short | WBP2 negatively regulates the Hippo pathway by competitively binding to WWC3 with LATS1 to promote non-small cell lung cancer progression |
title_sort | wbp2 negatively regulates the hippo pathway by competitively binding to wwc3 with lats1 to promote non-small cell lung cancer progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035140/ https://www.ncbi.nlm.nih.gov/pubmed/33837178 http://dx.doi.org/10.1038/s41419-021-03600-3 |
work_keys_str_mv | AT hanqiang wbp2negativelyregulatesthehippopathwaybycompetitivelybindingtowwc3withlats1topromotenonsmallcelllungcancerprogression AT rongxuezhu wbp2negativelyregulatesthehippopathwaybycompetitivelybindingtowwc3withlats1topromotenonsmallcelllungcancerprogression AT linxuyong wbp2negativelyregulatesthehippopathwaybycompetitivelybindingtowwc3withlats1topromotenonsmallcelllungcancerprogression AT zhangxiupeng wbp2negativelyregulatesthehippopathwaybycompetitivelybindingtowwc3withlats1topromotenonsmallcelllungcancerprogression AT fanchuifeng wbp2negativelyregulatesthehippopathwaybycompetitivelybindingtowwc3withlats1topromotenonsmallcelllungcancerprogression AT zhaohuanyu wbp2negativelyregulatesthehippopathwaybycompetitivelybindingtowwc3withlats1topromotenonsmallcelllungcancerprogression AT wangenhua wbp2negativelyregulatesthehippopathwaybycompetitivelybindingtowwc3withlats1topromotenonsmallcelllungcancerprogression |