机构：[1]Department of Breast and Thyroid Surgery, Changhai Hospital, Naval Military Medical University, Shanghai 200433, China[2]Department of Oncology, Third Affiliated Hospital of Naval Military Medical University, Shanghai 200438, China[3]Department of Hepatic Surgery, Third Affiliated Hospital of Naval Military Medical University, Shanghai 200438, China[4]Department of Neurosurgery, The First People’s Hospital of Yunnan Province, Kunming 650032, China外科片神经外科云南省第一人民医院[5]State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China[6]Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China[7]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Nogo-B has been reported to play a critical role in angiogenesis and the repair of damaged blood vessels; however, its role in the tumor microenvironment remains unclear. Here, we observed the differential expression of Nogo-B in endothelial cells from hepatocellular carcinoma (HCC) and glioma samples. Downregulation of Nogo-B expression correlated with the malignant phenotype of cancer and a poor prognosis for patients. In subsequent studies, endothelial Nogo-B inhibition robustly promoted the growth of HCC or glioma xenografts in nude mice. Intriguingly, endothelial Nogo-B silencing dramatically suppressed endothelial cell expansion and tumor angiogenesis, but potently enhanced the proliferation of neighboring HCC and glioma cells. Based on the results of the ELISA assay, Nogo-B silencing reduced TGF-beta production in endothelial cells, which attenuated the phosphorylation and nuclear translocation of Smad in neighboring cancer cells. The endothelial Nogo-B silencing-mediated increase in cancer cell proliferation was abolished by either a TGF-beta neutralizing antibody or TGF-beta receptor inhibitor, indicating the essential role for TGF-beta in endothelial Nogo-B-mediated suppression of cancer growth. These findings not only broaden our understanding of the crosstalk between cancer cells and endothelial cells but also provide a novel prognostic biomarker and a therapeutic target for cancer treatments.
基金：
National Natural Science Foundation of China [81972777]; National Natural Science Foundation of Shanghai [19ZR1400300, 18ZR1438600]
第一作者机构：[1]Department of Breast and Thyroid Surgery, Changhai Hospital, Naval Military Medical University, Shanghai 200433, China
共同第一作者：
通讯作者：
通讯机构：[6]Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China[7]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
推荐引用方式(GB/T 7714)：
Li Hengyu,Cheng Zhuo,Yang Pinghua,et al.Endothelial Nogo-B Suppresses Cancer Cell Proliferation via a Paracrine TGF-beta/Smad Signaling[J].CELLS.2022,11(19):doi:10.3390/cells11193084.
APA：
Li, Hengyu,Cheng, Zhuo,Yang, Pinghua,Huang, Wei,Li, Xizhou...&Wu, Xiaojun.(2022).Endothelial Nogo-B Suppresses Cancer Cell Proliferation via a Paracrine TGF-beta/Smad Signaling.CELLS,11,(19)
MLA：
Li, Hengyu,et al."Endothelial Nogo-B Suppresses Cancer Cell Proliferation via a Paracrine TGF-beta/Smad Signaling".CELLS 11..19(2022)
