Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1

Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with...

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Autores principales: Yankang Cui, Chenkui Miao, Shouyong Liu, Jingyuan Tang, Jing Zhang, Hengtao Bu, Yuhao Wang, Chao Liang, Meiling Bao, Chao Hou, Jiajin Wu, Xiaochao Chen, Xiang Zhang, Zengjun Wang, Bianjiang Liu
Formato: article
Lenguaje:EN
Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/5892ed501ea840abbc07b33ffcaf8bb9
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spelling oai:doaj.org-article:5892ed501ea840abbc07b33ffcaf8bb92021-11-22T04:23:58ZClusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a12162-253110.1016/j.omtn.2021.11.004https://doaj.org/article/5892ed501ea840abbc07b33ffcaf8bb92021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002791https://doaj.org/toc/2162-2531Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with tumor stage. Tcam-2 cell line was used to investigate the CLU function in testicular seminoma, and CLU was found to inhibit the proliferation and metastasis abilities. Besides, extracellular matrix protein COL15a1 was demonstrated as the downstream of CLU to affect the epithelial-mesenchymal transition (EMT) process via competitively binding to DDR1 with COL1A1 and inhibiting the phosphorylation of PYK2. MEF2A was found to interact with CLU and bind to the promoter of COL15a1 and so upregulate its expression. This is the first study using testicular xenografts in situ to simulate testicular seminoma metastatic and proliferative capacities. In conclusion, CLU acts as a tumor suppressor to inhibit the metastasis of testicular seminoma by interacting with MEF2A to upregulate COL15a1 and blocking the EMT process.Yankang CuiChenkui MiaoShouyong LiuJingyuan TangJing ZhangHengtao BuYuhao WangChao LiangMeiling BaoChao HouJiajin WuXiaochao ChenXiang ZhangZengjun WangBianjiang LiuElsevierarticleclusterinseminomaEMTCOL15a1MEF2Atesticular xenografts in situTherapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1336-1350 (2021)
institution DOAJ
collection DOAJ
language EN
topic clusterin
seminoma
EMT
COL15a1
MEF2A
testicular xenografts in situ
Therapeutics. Pharmacology
RM1-950
spellingShingle clusterin
seminoma
EMT
COL15a1
MEF2A
testicular xenografts in situ
Therapeutics. Pharmacology
RM1-950
Yankang Cui
Chenkui Miao
Shouyong Liu
Jingyuan Tang
Jing Zhang
Hengtao Bu
Yuhao Wang
Chao Liang
Meiling Bao
Chao Hou
Jiajin Wu
Xiaochao Chen
Xiang Zhang
Zengjun Wang
Bianjiang Liu
Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1
description Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with tumor stage. Tcam-2 cell line was used to investigate the CLU function in testicular seminoma, and CLU was found to inhibit the proliferation and metastasis abilities. Besides, extracellular matrix protein COL15a1 was demonstrated as the downstream of CLU to affect the epithelial-mesenchymal transition (EMT) process via competitively binding to DDR1 with COL1A1 and inhibiting the phosphorylation of PYK2. MEF2A was found to interact with CLU and bind to the promoter of COL15a1 and so upregulate its expression. This is the first study using testicular xenografts in situ to simulate testicular seminoma metastatic and proliferative capacities. In conclusion, CLU acts as a tumor suppressor to inhibit the metastasis of testicular seminoma by interacting with MEF2A to upregulate COL15a1 and blocking the EMT process.
format article
author Yankang Cui
Chenkui Miao
Shouyong Liu
Jingyuan Tang
Jing Zhang
Hengtao Bu
Yuhao Wang
Chao Liang
Meiling Bao
Chao Hou
Jiajin Wu
Xiaochao Chen
Xiang Zhang
Zengjun Wang
Bianjiang Liu
author_facet Yankang Cui
Chenkui Miao
Shouyong Liu
Jingyuan Tang
Jing Zhang
Hengtao Bu
Yuhao Wang
Chao Liang
Meiling Bao
Chao Hou
Jiajin Wu
Xiaochao Chen
Xiang Zhang
Zengjun Wang
Bianjiang Liu
author_sort Yankang Cui
title Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1
title_short Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1
title_full Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1
title_fullStr Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1
title_full_unstemmed Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1
title_sort clusterin suppresses invasion and metastasis of testicular seminoma by upregulating col15a1
publisher Elsevier
publishDate 2021
url https://doaj.org/article/5892ed501ea840abbc07b33ffcaf8bb9
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