Cargando…

Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer

Previous studies revealed that Asporin (ASPN) is a potential mediator in the development of various types of cancer as a secreted stroma protein, but the function of ASPN inside the cancer cells remains largely unknown. Here, we demonstrated a higher expression level of ASPN in colorectal cancer (CR...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Hengcun, Zhang, Zheng, Chen, Lei, Sun, Xiujing, Zhao, Yu, Guo, Qingdong, Zhu, Shengtao, Li, Peng, Min, Li, Zhang, Shutian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365561/
https://www.ncbi.nlm.nih.gov/pubmed/30728352
http://dx.doi.org/10.1038/s41419-019-1376-9
_version_ 1783393447077478400
author Li, Hengcun
Zhang, Zheng
Chen, Lei
Sun, Xiujing
Zhao, Yu
Guo, Qingdong
Zhu, Shengtao
Li, Peng
Min, Li
Zhang, Shutian
author_facet Li, Hengcun
Zhang, Zheng
Chen, Lei
Sun, Xiujing
Zhao, Yu
Guo, Qingdong
Zhu, Shengtao
Li, Peng
Min, Li
Zhang, Shutian
author_sort Li, Hengcun
collection PubMed
description Previous studies revealed that Asporin (ASPN) is a potential mediator in the development of various types of cancer as a secreted stroma protein, but the function of ASPN inside the cancer cells remains largely unknown. Here, we demonstrated a higher expression level of ASPN in colorectal cancer (CRC) than matched normal tissues, and 25% (2/8) CRC showed copy number variation (CNV) gain/amplification in ASPN gene. Both higher ASPN expression levels and ASPN CNV gain/amplification indicated a worse prognosis in CRC patients. ASPN can promote proliferation, migration, and invasion of CRC cells, and inhibit apoptosis by activating Akt/Erk and TGF-β/Smad2/3 signalings. Further investigations revealed that ASPN interacts with Smad2/3, facilitates its translocation into nucleus, and up-regulates the expression of Epithelial-mesenchymal transition (EMT) related genes. Rescue assays confirmed that TGF-β signaling is essential for the effects of ASPN on promoting CRC cell migration and invasion. In conclusion, ASPN promotes the migration and invasion of CRC cells via TGF-β/Smad2/3 pathway and could serve as a potential prognostic biomarker in CRC patients.
format Online
Article
Text
id pubmed-6365561
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-63655612019-02-07 Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer Li, Hengcun Zhang, Zheng Chen, Lei Sun, Xiujing Zhao, Yu Guo, Qingdong Zhu, Shengtao Li, Peng Min, Li Zhang, Shutian Cell Death Dis Article Previous studies revealed that Asporin (ASPN) is a potential mediator in the development of various types of cancer as a secreted stroma protein, but the function of ASPN inside the cancer cells remains largely unknown. Here, we demonstrated a higher expression level of ASPN in colorectal cancer (CRC) than matched normal tissues, and 25% (2/8) CRC showed copy number variation (CNV) gain/amplification in ASPN gene. Both higher ASPN expression levels and ASPN CNV gain/amplification indicated a worse prognosis in CRC patients. ASPN can promote proliferation, migration, and invasion of CRC cells, and inhibit apoptosis by activating Akt/Erk and TGF-β/Smad2/3 signalings. Further investigations revealed that ASPN interacts with Smad2/3, facilitates its translocation into nucleus, and up-regulates the expression of Epithelial-mesenchymal transition (EMT) related genes. Rescue assays confirmed that TGF-β signaling is essential for the effects of ASPN on promoting CRC cell migration and invasion. In conclusion, ASPN promotes the migration and invasion of CRC cells via TGF-β/Smad2/3 pathway and could serve as a potential prognostic biomarker in CRC patients. Nature Publishing Group UK 2019-02-06 /pmc/articles/PMC6365561/ /pubmed/30728352 http://dx.doi.org/10.1038/s41419-019-1376-9 Text en © The Author(s) 2019 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/.
spellingShingle Article
Li, Hengcun
Zhang, Zheng
Chen, Lei
Sun, Xiujing
Zhao, Yu
Guo, Qingdong
Zhu, Shengtao
Li, Peng
Min, Li
Zhang, Shutian
Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer
title Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer
title_full Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer
title_fullStr Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer
title_full_unstemmed Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer
title_short Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer
title_sort cytoplasmic asporin promotes cell migration by regulating tgf-β/smad2/3 pathway and indicates a poor prognosis in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365561/
https://www.ncbi.nlm.nih.gov/pubmed/30728352
http://dx.doi.org/10.1038/s41419-019-1376-9
work_keys_str_mv AT lihengcun cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT zhangzheng cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT chenlei cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT sunxiujing cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT zhaoyu cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT guoqingdong cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT zhushengtao cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT lipeng cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT minli cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer
AT zhangshutian cytoplasmicasporinpromotescellmigrationbyregulatingtgfbsmad23pathwayandindicatesapoorprognosisincolorectalcancer