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EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation

Bladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signa...

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Autores principales: Yin, Hubin, Zhang, Chen, Wei, Zongjie, He, Weiyang, Xu, Ning, Xu, Yingjie, Li, Tinghao, Ren, Ke, Kuang, Youlin, Zhu, Xin, Yuan, Fangchao, Yu, Haitao, Gou, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748695/
https://www.ncbi.nlm.nih.gov/pubmed/35013128
http://dx.doi.org/10.1038/s41419-021-04479-w
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author Yin, Hubin
Zhang, Chen
Wei, Zongjie
He, Weiyang
Xu, Ning
Xu, Yingjie
Li, Tinghao
Ren, Ke
Kuang, Youlin
Zhu, Xin
Yuan, Fangchao
Yu, Haitao
Gou, Xin
author_facet Yin, Hubin
Zhang, Chen
Wei, Zongjie
He, Weiyang
Xu, Ning
Xu, Yingjie
Li, Tinghao
Ren, Ke
Kuang, Youlin
Zhu, Xin
Yuan, Fangchao
Yu, Haitao
Gou, Xin
author_sort Yin, Hubin
collection PubMed
description Bladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer.
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spelling pubmed-87486952022-01-20 EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation Yin, Hubin Zhang, Chen Wei, Zongjie He, Weiyang Xu, Ning Xu, Yingjie Li, Tinghao Ren, Ke Kuang, Youlin Zhu, Xin Yuan, Fangchao Yu, Haitao Gou, Xin Cell Death Dis Article Bladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer. Nature Publishing Group UK 2022-01-10 /pmc/articles/PMC8748695/ /pubmed/35013128 http://dx.doi.org/10.1038/s41419-021-04479-w 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
Yin, Hubin
Zhang, Chen
Wei, Zongjie
He, Weiyang
Xu, Ning
Xu, Yingjie
Li, Tinghao
Ren, Ke
Kuang, Youlin
Zhu, Xin
Yuan, Fangchao
Yu, Haitao
Gou, Xin
EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation
title EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation
title_full EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation
title_fullStr EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation
title_full_unstemmed EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation
title_short EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation
title_sort egf-induced nuclear translocation of shcbp1 promotes bladder cancer progression through inhibiting racgap1-mediated rac1 inactivation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748695/
https://www.ncbi.nlm.nih.gov/pubmed/35013128
http://dx.doi.org/10.1038/s41419-021-04479-w
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