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.

中文翻译：

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Nogo-B通过增强Yap / Taz介导的肿瘤相关巨噬细胞M2极化促进HCC进程。

肿瘤相关巨噬细胞（TAM）及其M2型极大地促进了肿瘤的血管生成，侵袭和转移，包括肝细胞癌（HCC）。Nogo-B在大多数组织中表达，并参与巨噬细胞极化。但是，尚不清楚Nogo-B是否参与极化和TAM的作用。肝癌患者TAM中Nogo-B的表达显着增加，这与肝癌患者预后不良有关。巧合的是，HCC条件培养基（HCM）促进了Nogo-B表达和巨噬细胞的M2表型。Nogo-B抑制Nogo-B在体内和体外均能显着抑制巨噬细胞的M2型极化并抑制HCC细胞增殖。此外，Nogo-B的干扰促进了巨噬细胞介导的肿瘤细胞凋亡。Nogo-B有意义地增强了IL4刺激了巨噬细胞的替代激活以及具有PDZ结合基序的转录调节因子Yes相关蛋白（Yap）/转录共激活因子（Taz）的表达。Yap的抑制剂Verteporfin可阻止Nogo-B-Yap / Taz介导的巨噬细胞M2极化。巨噬细胞中的Nogo-B表达促进了与肿瘤相关的巨噬细胞M2极化和TAM在肝癌中的促癌作用。在巨噬细胞中靶向Nogo-B / Yap / Taz可以为HCC治疗提供新的治疗策略。可以阻止Nogo-B-Yap / Taz介导的巨噬细胞M2极化。巨噬细胞中的Nogo-B表达促进了与肿瘤相关的巨噬细胞M2极化和TAM在肝癌中的促癌作用。在巨噬细胞中靶向Nogo-B / Yap / Taz可以为HCC治疗提供新的治疗策略。可以阻止Nogo-B-Yap / Taz介导的巨噬细胞M2极化。巨噬细胞中的Nogo-B表达促进了与肿瘤相关的巨噬细胞M2极化和TAM在肝癌中的促癌作用。在巨噬细胞中靶向Nogo-B / Yap / Taz可以为HCC治疗提供新的治疗策略。