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Tytuł:
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Capn4 contributes to tumor invasion and metastasis in gastric cancer via activation of the Wnt/β-catenin/MMP9 signalling pathways.
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Autorzy:
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Zhao C; Department of General Surgery, Jiujiang First People's Hospital, Jiujiang, Jiangxi 332000, China.
Yuan G; Department of Hepatopancreatobiliary Surgery, Jiujiang First People's Hospital, Jiujiang, Jiangxi 332000, China.
Jiang Y; Department of prosthodontics, The Affiliated Stomatological Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, China.
Xu J; Department of Hepatopancreatobiliary Surgery, Jiujiang First People's Hospital, Jiujiang, Jiangxi 332000, China.
Ye L; Department of General Surgery, Jiujiang First People's Hospital, Jiujiang, Jiangxi 332000, China.
Zhan W; Department of Maxillofacial Surgery, The Affiliated Stomatological Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, China. Electronic address: .
Wang J; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address: .
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Źródło:
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Experimental cell research [Exp Cell Res] 2020 Oct 15; Vol. 395 (2), pp. 112220. Date of Electronic Publication: 2020 Aug 07.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Orlando Fl : Academic Press
Original Publication: New York, Academic Press.
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MeSH Terms:
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Calpain/*metabolism
Neoplasm Metastasis/*pathology
Stomach Neoplasms/*pathology
Wnt Signaling Pathway/*physiology
Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Matrix Metalloproteinase 9/metabolism ; Stomach Neoplasms/metabolism ; Up-Regulation
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Contributed Indexing:
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Keywords: Capn4; Gastric cancer; MMP9; Ubiquitination; β-Catenin
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Substance Nomenclature:
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EC 3.4.22.- (Calpain)
EC 3.4.22.52 (CAPNS1 protein, human)
EC 3.4.24.35 (MMP9 protein, human)
EC 3.4.24.35 (Matrix Metalloproteinase 9)
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Entry Date(s):
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Date Created: 20200811 Date Completed: 20210303 Latest Revision: 20210303
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Update Code:
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20240105
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DOI:
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10.1016/j.yexcr.2020.112220
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PMID:
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32777225
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Capn4, a small regulatory subunit of the calpain proteolytic system, functions as a potential tumor promoter in several cancers. However, the biological functions and molecular mechanisms of Capn4 in gastric cancer (GC) remain poorly understood. In the current study, we found that upregulation of Capn4 was detected frequently in GC tissues, and was associated with significantly worse survival among the GC patients. Multivariate analyses revealed that abundance of Capn4 was an independent predictive marker for the poor prognosis of GC. Further, Capn4 knockdown notably suppressed GC invasion and metastasis in vitro. Consistently, a xenograft assay showed that silencing of Capn4 in GC cells suppressed their dissemination to lung tissue in vivo. Moreover, our results indicated that Capn4 promotes gastric cancer metastasis by increasing MMP9 expression, and demonstrated that MMP9 is crucial for the pro-metastasis role of Capn4 in GC cells. Further investigation revealed that Capn4 regulated MMP9 expression via activation of Wnt/β-catenin signaling pathway. Mechanistically, we found that Capn4 can decreased β-catenin ubiquitination to enhance the protein stability of β-catenin in GC cells. Collectively, Capn4 has a central role in gastric cancer metastasis, which could be a potential diagnostic and therapeutic target for GC.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
