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LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling

LIM and SH3 protein 1(LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the mechanism remains unclear. Here, we show that LASP1 interacts with S100 calcium binding protein A11(S100A11) and enhances its expression in CRC. LASP1-S100A11 axis is essential for TGFβ-mediated epit...

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Autores principales: Niu, Ya, Shao, Ziyun, Wang, Hui, Yang, Jiaqi, Zhang, Feifei, Luo, Yuhao, Xu, Lijun, Ding, Yanqing, Zhao, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867635/
https://www.ncbi.nlm.nih.gov/pubmed/27181092
http://dx.doi.org/10.1038/srep26112
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author Niu, Ya
Shao, Ziyun
Wang, Hui
Yang, Jiaqi
Zhang, Feifei
Luo, Yuhao
Xu, Lijun
Ding, Yanqing
Zhao, Liang
author_facet Niu, Ya
Shao, Ziyun
Wang, Hui
Yang, Jiaqi
Zhang, Feifei
Luo, Yuhao
Xu, Lijun
Ding, Yanqing
Zhao, Liang
author_sort Niu, Ya
collection PubMed
description LIM and SH3 protein 1(LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the mechanism remains unclear. Here, we show that LASP1 interacts with S100 calcium binding protein A11(S100A11) and enhances its expression in CRC. LASP1-S100A11 axis is essential for TGFβ-mediated epithelial-mesenchymal transition (EMT) and cell aggressive phenotype. Clinically, S100A11 is overexpressed in CRC tissues and localized in both the cytoplasm and the nucleus of CRC cells. Overexpression of S100A11 in cytoplasmic and nuclear subcellular compartments is associated with tumor metastasis and poor prognosis of CRC patients. Introduction of cytoplasmic and nuclear S100A11 promotes aggressive phenotypes of CRC cells in vitro as well as growth and metastasis of CRC xenografts, whereas suppressing S100A11 abrogates these effects. Furthermore, we identify flotillin-1 (FLOT1) and histone H1 as downstream factors for cytoplasmic and nuclear pathway of S100A11, which are required for LASP1-S100A11 axis-mediated EMT and CRC progression. These findings indicate S100A11, combined with LASP1, plays a critical role in promoting CRC metastasis via its subcellular effectors, FLOT1 and histone H1.
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spelling pubmed-48676352016-05-31 LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling Niu, Ya Shao, Ziyun Wang, Hui Yang, Jiaqi Zhang, Feifei Luo, Yuhao Xu, Lijun Ding, Yanqing Zhao, Liang Sci Rep Article LIM and SH3 protein 1(LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the mechanism remains unclear. Here, we show that LASP1 interacts with S100 calcium binding protein A11(S100A11) and enhances its expression in CRC. LASP1-S100A11 axis is essential for TGFβ-mediated epithelial-mesenchymal transition (EMT) and cell aggressive phenotype. Clinically, S100A11 is overexpressed in CRC tissues and localized in both the cytoplasm and the nucleus of CRC cells. Overexpression of S100A11 in cytoplasmic and nuclear subcellular compartments is associated with tumor metastasis and poor prognosis of CRC patients. Introduction of cytoplasmic and nuclear S100A11 promotes aggressive phenotypes of CRC cells in vitro as well as growth and metastasis of CRC xenografts, whereas suppressing S100A11 abrogates these effects. Furthermore, we identify flotillin-1 (FLOT1) and histone H1 as downstream factors for cytoplasmic and nuclear pathway of S100A11, which are required for LASP1-S100A11 axis-mediated EMT and CRC progression. These findings indicate S100A11, combined with LASP1, plays a critical role in promoting CRC metastasis via its subcellular effectors, FLOT1 and histone H1. Nature Publishing Group 2016-05-16 /pmc/articles/PMC4867635/ /pubmed/27181092 http://dx.doi.org/10.1038/srep26112 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Niu, Ya
Shao, Ziyun
Wang, Hui
Yang, Jiaqi
Zhang, Feifei
Luo, Yuhao
Xu, Lijun
Ding, Yanqing
Zhao, Liang
LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling
title LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling
title_full LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling
title_fullStr LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling
title_full_unstemmed LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling
title_short LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling
title_sort lasp1-s100a11 axis promotes colorectal cancer aggressiveness by modulating tgfβ/smad signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867635/
https://www.ncbi.nlm.nih.gov/pubmed/27181092
http://dx.doi.org/10.1038/srep26112
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