Ribosomal protein S15a promotes tumor angiogenesis via enhancing Wnt/β-catenin-induced FGF18 expression in hepatocellular carcinoma
| العنوان: | Ribosomal protein S15a promotes tumor angiogenesis via enhancing Wnt/β-catenin-induced FGF18 expression in hepatocellular carcinoma |
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| المؤلفون: | Yi Wang, Fuxiang Yu, Pengyi Guo, Qiandong Zhu, Fang Wu, Rongyuan Zheng, Zhengping Yu, Chunxiu Dai, Xiaozai Xie, Yun-feng Shan, Chonglin Tao, Gang Chen, Haitao Yu, Renumathy Dhanasekaran, Junjian Li, Long-Yun Ye |
| المصدر: | Oncogene. 37:1220-1236 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cancer Research, Angiogenesis, Apoptosis, Fibroblast growth factor, Neovascularization, Mice, 0302 clinical medicine, Tumor Cells, Cultured, beta Catenin, Mice, Inbred BALB C, Neovascularization, Pathologic, Liver Neoplasms, Wnt signaling pathway, Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, Survival Rate, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Female, medicine.symptom, Adult, Ribosomal Proteins, Carcinoma, Hepatocellular, Mice, Nude, Wnt1 Protein, Biology, 03 medical and health sciences, Paracrine signalling, Biomarkers, Tumor, Genetics, medicine, Animals, Humans, Neoplasm Invasiveness, Molecular Biology, Protein kinase B, Aged, Cell Proliferation, Tumor microenvironment, Xenograft Model Antitumor Assays, digestive system diseases, Fibroblast Growth Factors, 030104 developmental biology, Case-Control Studies, Catenin, Cancer research, Follow-Up Studies |
| الوصف: | Ribosomal protein s15a (RPS15A) plays a promotive role in the mRNA/ribosome interactions during early translation. Our previous study has found that inhibiting RPS15A expression can decrease proliferation and induce cell cycle arrest in hepatocellular carcinoma (HCC) cell lines. However, the mechanism underlying the involvement of RPS15A in HCC pathogenesis and the clinical significance of RPS15A expression remain unclear. In this study, an evaluation of RPS15A expression in 110 surgically resected HCCs and matched tumor-adjacent normal tissues revealed an overexpression of RPS15A in HCC, which was correlated with worse survival. In addition, tumor tissue with higher RPS15A expression demonstrated a higher microvascular density (MVD). Subsequently, two HCC cell lines, Huh7 (low-level constitutive RPS15A expression) and HepG2 (high RPS15A expression) were used to further evaluate the role of RPS15A in angiogenesis. The co-culture experiment of HCC cells with endothelial cells revealed that the induced overexpression of RPS15A in Huh7 cells increased the angiogenic potential of HUVEC in a paracrine fashion; conversely, knockdown of RPS15A in HepG2 cells showed an opposite effect. Further analysis indicated that RPS15A modulated FGF signaling by enhancing Wnt/beta-catenin-mediated FGF18 expression in HCC cells. FGF18, in turn, through binding to its FGFR3 receptor on endothelial cells, can activate the AKT and ERK pathway and promotes angiogenesis in a tumor microenvironment. Our in vivo experiment further confirmed that inhibition of RPS15A expression in HCC xenografts dramatically hindered tumor growth and inhibited tumor angiogenesis. Together, our findings suggest that RPS15A promotes angiogenesis in HCCs by enhancing Wnt/beta-catenin induced FGF18 expression. The RPS15A/FGF18 pathway may be a rational target for anti-angiogenic therapy of HCC. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f065369a6c3797cccccbb707f4e4079dTest https://doi.org/10.1038/s41388-017-0017-yTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....f065369a6c3797cccccbb707f4e4079d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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