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Tytuł:
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Nogo-B fosters HCC progression by enhancing Yap/Taz-mediated tumor-associated macrophages M2 polarization.
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Autorzy:
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Zhao X; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University of Chongqing, 400010, PR China.
Wang X; Department of Anesthesia, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China.
You Y; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University of Chongqing, 400010, PR China.
Wen D; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University of Chongqing, 400010, PR China.
Feng Z; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University of Chongqing, 400010, PR China.
Zhou Y; Department of Hepatobiliary Surgery, People's Hospital of Kaizhou, Chongqing, 400010, PR China.
Que K; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University of Chongqing, 400010, PR China.
Gong J; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University of Chongqing, 400010, PR China.
Liu Z; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University of Chongqing, 400010, PR China. Electronic address: .
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Źródło:
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Experimental cell research [Exp Cell Res] 2020 Jun 01; Vol. 391 (1), pp. 111979. Date of Electronic Publication: 2020 Apr 01.
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Typ publikacji:
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Journal Article
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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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Gene Expression Regulation, Neoplastic*
Adaptor Proteins, Signal Transducing/*genetics
Carcinoma, Hepatocellular/*genetics
Liver Neoplasms/*genetics
Receptors, Cell Surface/*genetics
Trans-Activators/*genetics
Transcription Factors/*genetics
Tumor-Associated Macrophages/*metabolism
Adaptor Proteins, Signal Transducing/antagonists & inhibitors ; Adaptor Proteins, Signal Transducing/metabolism ; Aged ; Animals ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/mortality ; Carcinoma, Hepatocellular/surgery ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Disease Progression ; Female ; Humans ; Interleukin-4/genetics ; Interleukin-4/metabolism ; Liver Neoplasms/diagnosis ; Liver Neoplasms/mortality ; Liver Neoplasms/surgery ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Prognosis ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Receptors, Cell Surface/antagonists & inhibitors ; Receptors, Cell Surface/metabolism ; Signal Transduction ; Survival Analysis ; Trans-Activators/metabolism ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/metabolism ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; Tumor-Associated Macrophages/drug effects ; Tumor-Associated Macrophages/pathology ; Verteporfin/pharmacology ; Xenograft Model Antitumor Assays ; YAP-Signaling Proteins
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Contributed Indexing:
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Keywords: HCC; M2-type polarization; Nogo-B; TAMs; Yap/Taz
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Substance Nomenclature:
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0 (Adaptor Proteins, Signal Transducing)
0 (IL4 protein, human)
0 (NUS1 protein, human)
0 (RNA, Small Interfering)
0 (Receptors, Cell Surface)
0 (Trans-Activators)
0 (Transcription Factors)
0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins)
0 (WWTR1 protein, human)
0 (YAP-Signaling Proteins)
0 (YAP1 protein, human)
0X9PA28K43 (Verteporfin)
207137-56-2 (Interleukin-4)
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Entry Date(s):
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Date Created: 20200405 Date Completed: 20201209 Latest Revision: 20211204
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Update Code:
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20240105
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DOI:
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10.1016/j.yexcr.2020.111979
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PMID:
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32246992
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Tumor-associated macrophages (TAMs) and their M2-type extremely promote tumor angiogenesis, invasion and metastasis, including hepatocellular carcinoma (HCC). Nogo-B is expressed in most tissues and participates in macrophage polarization. However, whether Nogo-B is involved in the polarization and the effects of TAMs has been unclear. The expression of Nogo-B in TAMs of HCC patients is significantly increased, which correlated with the poor prognosis of the patients with HCC. Coincidentally, HCC conditioned medium (HCM) facilitated Nogo-B expression and the M2 phenotype of macrophages. Nogo-B knockdown Nogo-B significantly suppressed the M2-type polarization of macrophages and inhibited HCC cells proliferation both in vivo and in vitro. Furthermore, interference of Nogo-B facilitates macrophage-mediated apoptosis of tumor cells. Nogo-B meaningfully enhanced IL4-stimulated the alternative activation of macrophages as well as expression of the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (Taz). An inhibitor of Yap, Verteporfin, could block Nogo-B-Yap/Taz-mediated macrophages M2 polarization. Nogo-B expression in macrophages facilitates tumor-associated macrophages M2 polarization and protumoral effects of TAMs in HCC. Targeting Nogo-B/Yap/Taz in macrophages could provide a new therapeutic strategy in HCC therapy.
Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.
(Copyright © 2020 Elsevier Inc. All rights reserved.)